Selective serotonin reuptake inhibitors (SSRI) have been claimed to negatively affect the thyroid function, albeit the evidence is controversial. We searched for studies that measured parameters of thyroid function (TSH, T4, Free T4, or T3) before and after a course of SSRI treatment in euthyroid patients with major depressive disorder. Electronic searches were conducted on MEDLINE, Embase and Web of Science databases from inception through April 4th, 2018. We performed random-effects meta-analyses to estimate the effect of SSRIs on each hormone. A total 1791 records were identified in the electronic search, and 14 observational clinical studies were included in the analyses. All studies had at least moderate risk of bias and were considered of low quality. A course of SSRI treatment was associated with a decrease in T4 of -6.58 nmol/L (95% Confidence Interval [CI], -12.17 to -.99, p = .005, I=97%; Cohen’s d = .50), a decrease in Free T4 of -.91 pmol/L (95% CI, -1.65 to -.16, p = .017, I=96%; Cohen’s d = .66), and a decrease in T3 of -.10 nmol/L (95% CI, -.18 to -.03, p = .007, I=96%; Cohen’s d = .45), and no effect on TSH (0.06 microIU/L, 95% CI, -.05 to .17, p = .285, I=98%; Cohen’s d = .17). We did not detect publication bias in any of the four meta-analyses. We conclude that there is preliminary evidence that SSRIs slightly decrease thyroid function, but quality of evidence is low. Clinical magnitude of such effect is yet unclear.Copyright © 2020. Published by Elsevier B.V.