Background: Exposure to disinfectants and disinfection byproducts (DBPs) due to swimming in chlorinated water has been associated with allergic and respiratory health effects, including asthma. Objectives: Biological mechanisms contributing to these associations are largely unknown. We hypothesized a potential pathway involving modulation of the immune system. Methods: We assessed levels of immune markers (CCL11, CCL22, CXCL10, CRP, EGF, GCSF, IL-8, IL-17, IL-1RA, MPO, VEGF, Periostin) in serum collected from 30 women and 29 men before and after 40min of swimming in a chlorinated pool. Exposure to DBPs was assessed by measuring bromodichloromethane, bromoform, chloroform, and dibromochloromethane in exhaled breath before and after swimming. Covariate data including information on physical activity was available through questionnaires and measurements. We assessed the association between indicators of swimming in a chlorinated pool and changes in serum immune marker concentrations using linear regression with bivariate normal distributions and adjusted for multiple comparisons by applying the Benjamini-Hochberg procedure. Results: We observed a significant decrease in serum concentrations of IL-8 (−12.53%; q=2.00e-03), CCL22 (−7.28%; q=4.00e-04), CCL11 (−7.15%; q=9.48e-02), CRP (−7.06%; q=4.68e-05), and CXCL10 (−13.03%; q=6.34e-14) and a significant increase in IL-1RA (20.16%; q=4.18e-06) from before to after swimming. Associations with quantitative measurements of DBPs or physical activity were similar in direction and strength. Most of the observed associations became non-significant when we adjusted the effects of exposure to DBPs for physical activity or vice-versa. Conclusions: Our study indicates that swimming in a chlorinated pool induces perturbations of the immune response through acute alterations of patterns of cytokine and chemokine secretion. The observed effects could not be uniquely attributed to either exposure to DBPs or physical activity. Evidence in the literature suggests that observed decreases in immune markers are possibly due to an immunosuppressive effect of DBPs, while the increase in IL-1RA might be due to physical activity. Keywords: Immune markers, Disinfection byproducts, DBPs, Blood