Background: Depression is one of the most serious social problems that has led to an increase in the use of antidepressants over the past two decades. Paroxetine is one of the most widely used antidepressants categorized as a selective serotonin reuptake inhibitor, which is highly effective in treating depression. Despite the benefits of paroxetine, this drug affects the hypothalamus-pituitary-gonadal axis by increasing serotonin levels and reducing gonadotropin secretion, Follicle-stimulating hormone, Luteinizing hormone, and testosterone hormones, which adversely affects men's sexual performance and reduces male fertility. Objective: Considering the high prescription rate of paroxetine in treating depression in men, this study aimed to investigate the effect of paroxetine on sperm motility, viability, and morphology. Materials and Methods: This study was conducted on the sperm samples of 30 normal fertile men. The samples were divided into three groups: fresh, control, and the group treated with 5 µM paroxetine for 1 hr. The mean percentage of sperm motility was determined by optical microscope, the mean percentage of sperm viability was measured using eosin-nigrosin staining, and the morphology of sperm was examined using Diff-Quick staining. Results: The mean sperm motility, mean viability, and the mean percentage of sperm with a normal morphology showed a significant decrease in the paroxetine group compared to the fresh and control groups (p < 0.001). Conclusion: Our study showed that paroxetine reduces the motility, normal morphology, and viability of sperm by destroying mitochondria and increasing reactive oxygen species.
