Cadmium (Cd) is expected to cause deleterious effects on most organs, especially on the male reproductive system. The current study was performed to assess the effect of Cd on fertility in Swiss mice and to evaluate the protective role of caffeic acid phenethyl ester (CAPE) in relieving the detrimental effect of Cd. The mice were divided into four groups of 10: normal Group I received distilled water. Group II, III, and IV were injected 3 mg/kg body weight with Cd intraperitoneally for four consecutive days. Group III received saline. Group IV was treated with 3 mg/kg/day CAPE intraperitoneally for 6 days. Results indicated that CAPE brings about a highly significant improvement in fertility parameters, spermatogenesis, and reduced apoptotic percent. Moreover, metalloprotease-3 (MMP-3) and vascular endothelial growth factor reduced significantly. Overall, our results strongly suggest that CAPE has a protective effect, counteracts the toxic effects of Cd, and prevents testicular injury.