BACKGROUND: The literature on the relationship between lifestyle behaviors and inflammatory markers is scarce. METHODS: A birth cohort was followed since birth up to 22 years in Southern Brazil. Interleukin-6 (IL-6), C-reactive protein (CRP) and adiponectin were measured in nonfasting blood samples drawn at 18 and 22 years of age. Exposures including smoking, alcohol intake, physical inactivity and obesity, were collected at 15, 18 and 22 years. Cross sectional analyses were based on the number of follow-up visits with these exposures and the association with IL-6, CRP and adiponectin at 22 years old. We also carried out a longitudinal Generalized Least Squares (GLS) random-effects analysis with outcomes at 18 and at 22 years old. All analyses were adjusted for several covariates. RESULTS: The sample comprised 3,479 cohort members at 22 years. The presence of obesity at ≥ 2 follow-ups showed the highest mean values (SE) for IL-6 [2.45 (1.05)] and CRP [3.74 (1.11)] and the lowest mean value for adiponectin [8.60 (0.37)] (adjusted analyses, females) compared with other exposures; the highest mean of IL-6 [1.65 (1.05)] and CRP [1.78 (1.11)] and the lowest mean of adiponectin [9.98 (0.38)] were for the number of follow-ups with ≥2 exposures compared to those with no exposures at any follow-up (adjusted analyses, females). The longitudinal analysis showed an increase in obesity associated with IL-6 and CRP in both sexes and an inverse association with adiponectin in females; smoking (in males) was associated with IL-6 and CRP, harmful alcohol intake was associated with CRP in males, and increased in physical activity was inversely associated with CRP in men. CONCLUSION: We concluded that obesity is the main exposure positively associated with IL-6 and CRP and inversely associated with adiponectin (mainly in females). Smoking is also associated with these markers in the longitudinal analysis (in males).