The objective of this study was to investigate the role of glutathione depletion in fertility in rats. Forty male Sprague Dawley rats were divided into two groups. Twenty rats administered paracetamol (glutathione depletory) and the rest (the control) received 0.9% normalized saline for 90 days. At day 15, 30, 60, and 94 rats from each group were assessed for semen quality, sperm motility, morphology, glutathione concentration and histology of testis, liver and epididymis. The quality of semen was highly affected in the study group with semen homogeneity disappearing and liquefaction happening as early as 30 seconds, sperm motility, progressiveness and glutathione levels dropped, sperm abnormalities rose. Glutathione depletion affects male fertility especially on the quality of sperms affecting ability of the sperm to fertilize the egg. Abnormal mid-piece and tail were the most affected. 90 days post treatment, libido; mounting and intromission were also significantly affected.