Aim:To assess the effect of stress of examination on serum cortisol level and CD4 cell count in young male students at Igbinedion University. Methods: A cross sectional laboratory based analysis was adopted for this study. A total of 204 male undergraduate volunteers (age 22 + 1.0 years, body mass index 23 + 0.5 kg/m 2 ) were randomly recruited for the study. Total white blood cell (TWBC) was determined using the sysmex® Automated Hematology Analyzer. CD4 cell count was estimated using Partec cyflow counter, while serum cortisol level was determined by enzyme linked immuno sorbent assay technique. Results: There was a significant increase (P < 0.05) in the serum cortisol level at Stage A (1 st day of the semester) when compared with Stage B (midway in the semester) and Stage C (morning of the examination), while there was significant decrease (P < 0.05) in the TWBC count and CD4 cell count at Stage A when compared with Stage B and Stage C. Conclusion: The stress of examination inhibits proliferation of CD4 cells with the elevation of serum cortisol as a possible mediator.