The purpose of this investigation was to determine the effects of caffeine supplementation on caffeine tolerant and caffeine naïve individual’s lymphocyte counts, apoptosis and migration levels. In addition, effects of exercise on post-caffeine ingestion lymphocyte counts, apoptosis and migration levels were determined. It was hypothesized that caffeine would alter the immune system cell counts, but that exercise would be able to restore the immune system to homeostasis. Seventeen Western Kentucky University students were tested (males n=7, females n=10; n=7: caffeine tolerant= 200mg or more per day group, n=9: caffeine naïve= 50mg or less per day group). In this double-blind investigation, all participants completed two exercise bouts: 30 min of treadmill running at 60-80% HRR once with a placebo drink before exercise and once with 6 mg/kg body weight of caffeine drink completed in a counterbalanced manner. Blood was taken at rest, 30 min after drink ingestion, immediately post exercise, and 60 min post exercise. Blood was stained with antibody markers (Annexin V to determine apoptotic cell counts, CX3CR1 to determine cell migration, CD4=helper T cells, CD8=cytotoxic T cells, CD19=B cells). Blood was analyzed using flow cytometry. We found that cytotoxic T cells showed significant increases following the caffeinated run in both groups combined (tolerant and naïve, p=0.001) and specifically in the naïve group on the caffeine run (p=.004). We did not see any significant changes in CD4, or CD19 cell counts. There were no significant changes in CD4, CD8 or CD19 cell migration or apoptosis. Our results showed that caffeine supplementation causes an increased effect on cytotoxic T cells counts when combined with exercise, and this effect was greater for the caffeine naïve group. The combined effects of caffeine and exercise may have elevated the plasma catecholamine and cortisol levels which are associated with immune cell function and movement. CD8 cells have a greater density of β-receptors, which are influenced by catecholamine, and may explain the increase in their cell counts compared to CD4 and CD19.