Exercise-induced muscle damage may influence the immune response to exercise by altering circulating leukocyte subsets and limiting availability of glutamine (a crucial energy and biosynthetic substrate for leukocytes). The aim of this study was to determine whether the blood leukocyte, cortisol, and glutamine responses to eccentric exercise differed between females responding to exercise with high (High CK, n=7) and low (Low CK, n=5) serum creatine kinase activity (CK), an indirect marker of muscle damage. Maximal eccentric flexion and extension actions with one elbow (50 reps) and one knee (60 reps) were performed using a Biodex dynamometer. Blood was collected 1 d and 0 h pre-, 0 and 2 h, and 1, 2, 3, 5, 7 and 9 d post-exercise. Natural killer (NK), T helper (CD4), T cytotoxic (CD8) and B cells, monocytes, and granulocytes were analyzed. CK 5 d post-exercise was 2515 ± 2320 for High CK and 98± 68 for Low CK groups. NK cell concentration increased 25% in the High CK group (from 0.16 ± 0.05 to 0.20 ± 0.07 × 109 cells·L-1) 0 h post-exercise but not in the Low CK group (from 0.10 ± 0.04 to 0.11± 0.02 × 109 cells·L-1). Both groups had elevations (p<0.05) in granulocytes 0 and 2 h post-exercise despite decreased (p<0.01) serum cortisol at these same times. Cortisol generally increases granulocytes and decreases lymphocytes in the circulation. An index of immunocompetence, the CD4/CD8 ratio was lower (p<0.05) 0 h, 2 and 5 to 9 d post-exercise for both groups. B cells and monocytes were unchanged. Glutamine was lower (p<0.05) for both groups 2 d post-exercise, indicating increased utilization or decreased release from muscle. Thus, the NK cell response differed between groups, but granulocyte, CD4, CD8, cortisol, and glutamine responses following exercise were independent of post-exercise CK.