Abstract: Background and Objective: Infertility and maternal stress studies have become major public health problems in most societies and this has attracted urgent global attention. This study examined the modulatory role of restraint-induced stress and clomiphene citrate (CC) administration on the reproductive programming of Wistar rats. Materials and Methods: A total of 119 healthy Wistar rats weighing between 150-200 g were used and assigned into four major groups. Stress was induced for 1, 2, 4 and 6 hrs daily by exposure of the rats to a restraint plastic chamber for 1 and 2 weeks, respectively. At the end of each experimental protocol, the animals were euthanized by cervical dislocation and serum samples were collected for hormonal assay. The average gestational length, litter size and pup weight were examined. Data were expressed as Mean±SEM and mean differences were analyzed using One-way (ANOVA) and LSD post hoc Test with SPSS 23 at p<0.05 level of significance. Results: These findings showed that restraint stress caused a significant elevation in corticosterone level, while estrogen, progesterone, follicle-stimulating hormone and luteinizing hormone were significantly reduced when compared with control. Gestation length and litter size were also significantly reduced by stress while pup weights were not significantly affected. The CC increased litter size in unstressed rats when compared to litters of stressed rats that were significantly reduced, although, CC was able to increase the litter size of stressed rats towards normal. Conclusion: Evidence indicated that stress alters reproductive potential in female rats and also, reduces the effectiveness of CC in inducing ovulation.