OPKO Health Inc.

Major Shareholding Notification • Feb 22, 2021

FORM 4

UNITED STATES SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

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Check this box if no longer subject to Section 16. Form 4 or

Form 5 obligations may STATEMENT OF CHANGES IN BENEFICIAL OWNERSHIP OF SECURITIES

continue. See Instruction 1(b).

Filed pursuant to Section 16(a) of the Securities Exchange Act of 1934 or Section 30(h) of the Investment Company Act of 1940

FROST	1. Name and Address of Reporting Person PHILLIP M.D. ET AL		2. Issuer Name and Ticker or Trading Symbol OPKO Health, Inc. [OPK]	5. Relationship of Reporting Person(s) to Issuer (Check all applicable) X X Director 10% Owner
(Last) OPKO Health, Inc. 4400 Biscayne Blvd.	(First)	(Middle)	3. Date of Earliest Transaction (Month/Day/Year) 02/19/2021	Officer (give title below)____ Other (specify below) X CEO & Chairman
(Street) Miami (City)	FL (State)	33137 (Zip)	4. If Amendment, Date Original Filed (Month/Day/Year)	6. Individual or Joint/Group Filing (Check Applicable Line) ____ Form filed by One Reporting Person X Form filed by More than One Reporting Person

Table I - Non-Derivative Securities Acquired, Disposed of, or Beneficially Owned

1.Title of Security (Instr. 3)	2. Transaction Date (Month/Day/Year)	2A. Deemed Execution Date, if any	3. Transaction Code (Instr. 8)		(Instr. 3, 4 and 5)	4. Securities Acquired (A) or Disposed of (D)		5. Amount of Securities Beneficially Owned Following Reported Transaction(s)	6. Ownership Form:	7. Nature of Indirect Beneficial
		(Month/Day/Year)	Code	V	Amount	(A) or (D)	Price	(Instr. 3 and 4)	Direct (D) or Indirect (I) (Instr. 4)	Ownership (Instr. 4)
Common Stock								3,068,951	D
Common Stock	02/19/2021		P		8,700	A	\$4.71	191,380,394	I	See Footnote (1)
Common Stock	02/19/2021		P		3,496	A	\$4.715	191,383,890	I	See Footnote (1)
Common Stock	02/19/2021		P		24,204	A	\$4.72	191,408,094	I	See Footnote (1)
										See

Common Stock	02/19/2021	P	1,000	A	\$4.725	191,409,094	I	See Footnote (1)
Common Stock	02/19/2021	P	17,589	A	\$4.73	191,426,683	I	See Footnote (1)
Common Stock	02/19/2021	P	10,204	A	\$4.735	191,436,887	I	See Footnote (1)
Common Stock	02/19/2021	P	73,207	A	\$4.74	191,510,094	I	See Footnote (1)
Common Stock	02/19/2021	P	1,320	A	\$4.745	191,511,414	I	See Footnote (1)
Common Stock	02/19/2021	P	27,262	A	\$4.75	191,538,676	I	See Footnote (1)
Common Stock	02/19/2021	P	15,179	A	\$4.755	191,553,855	I	See Footnote (1)
Common Stock	02/19/2021	P	39,845	A	\$4.76	191,593,700	I	See Footnote (1)
Common Stock	02/19/2021	P	72,400	A	\$4.77	191,666,100	I	See Footnote (1)
Common Stock	02/19/2021	P	528	A	\$4.775	191,666,628	I	See Footnote (1)
Common Stock	02/19/2021	P	50,883	A	\$4.78	191,717,511	I	See Footnote (1)
Common Stock	02/19/2021	P	5,924	A	\$4.785	191,723,435	I	See Footnote (1)
								See

Common Stock	02/19/2021	P	44,745	A	\$4.79	191,768,180	I	Footnote (1)
Common Stock	02/19/2021	P	1,520	A	\$4.795	191,769,700	I	See Footnote (1)
Common Stock	02/19/2021	P	72,300	A	\$4.8	191,842,000	I	See Footnote (1)
Common Stock	02/19/2021	P	892	A	\$4.805	191,842,892	I	See Footnote (1)
Common Stock	02/19/2021	P	28,802	A	\$4.81	191,871,694	I	See Footnote (1)
Common Stock						30,127,177	I	See Footnote (2)

Table II - Derivative Securities Acquired, Disposed of, or Beneficially Owned (e.g., puts, calls, warrants, options, convertible securities)

1. Title of Derivative Security (Instr. 3)	2. Conversion or Exercise Price of Derivative Security	3. Transaction Date (Month/Day/Year)	3A. Deemed Execution Date, if any (Month/Day/Year)	4. Transaction Code (Instr. 8)		5. Number of Derivative Securities Acquired (A) or Disposed of (D) (Instr. 3, 4, and 5)		6. Date Exercisable and Expiration Date (Month/Day/Year)		7. Title and Amount of Underlying Securities (Instr. 3 and 4)		8. Price of Derivative Security (Instr. 5)	9. Number of Derivative Securities Beneficially Owned Following Reported Transaction(s)	10. Ownership Form of Derivative Security: Direct (D) or Indirect (I)	11. Nature of Indirect Beneficial Ownership (Instr. 4)
				Code	V	(A)	(D)	Date Exercisable	Expiration Date	Title	Amount or Number of Shares		(Instr. 4)	(Instr. 4)
Stock Option (Right to Buy)	\$4.81	02/19/2021		A		400,000		(3)	02/18/2031	Common Stock	400,000	\$ 0	400,000	D

	Relationships
Reporting Owner Name / Address	Director	10% Owner	Officer	Other
FROST PHILLIP M.D. ET AL OPKO Health, Inc. 4400 Biscayne Blvd. Miami, FL 33137	X	X	CEO & Chairman
Frost Gamma Investments Trust 4400 Biscayne Blvd. Miami, FL 33137		X

Explanation of Responses:

• (1) The securities are held by Frost Gamma Investments Trust, of which Phillip Frost M.D., is the trustee. Frost Gamma L.P. is the sole and exclusive beneficiary of Frost Gamma Investments Trust. Dr. Frost is one of two limited partners of Frost Gamma L.P. The general partner of Frost Gamma L.P. is Frost Gamma, Inc., and the sole shareholder of Frost Gamma, Inc. is Frost-Nevada Corporation. Dr. Frost is also the sole shareholder of Frost-Nevada Corporation. The reporting person disclaims beneficial ownership of these securities, except to the extent of any pecuniary interest therein and this report shall not be deemed an admission that the reporting person is the beneficial owner of these securities for purposes of Section 16 or for any other purpose.
• (2) These securities are held by Frost Nevada Investments Trust, of which the Reporting Person is the trustee and Frost-Nevada, L.P. is the sole and exclusive beneficiary. The Reporting Person is one of five limited partners of Frost-Nevada, L.P. and the sole shareholder of Frost-Nevada

Corporation, the sole general partner of Frost-Nevada, L.P. The reporting person disclaims beneficial ownership of these securities, except to the extent of any pecuniary interest therein and this report shall not be deemed an admission that the reporting person is the beneficial owner of these securities for purposes of Section 16 or for any other purpose.

(3) This option will vest in four equal annual installments beginning February 19, 2022.

Phillip Frost, M.D., Individually and as Trustee 02/22/2021

**Signature of Reporting Person Date

* If the form is filed by more than one reporting person, see Instruction 4(b)(v).

** Intentional misstatements or omissions of facts constitute Federal Criminal Violations. See 18 U.S.C. 1001 and 15 U.S.C. 78ff(a).

Note: File three copies of this Form, one of which must be manually signed. If space is insufficient, see Instruction 6 for procedure.

Potential persons who are to respond to the collection of information contained in this form are not required to respond unless the form displays a currently valid OMB number.

JOINT FILER INFORMATION

Name: Frost Gamma Investments Trust

Address: 4400 Biscayne Blvd. Miami, FL 33137

Designated Filer: Phillip Frost, M.D.

Issuer Name and Ticker Symbol: OPKO Health, Inc. (OPK)

Date of Earliest Transaction: February 19, 2021

Relationship to Issuer: 10% Owner

FROST GAMMA INVESTMENTS TRUST

By: /s/ Phillip Frost, M.D., as Trustee Phillip Frost, M.D., Trustee