We investigated whether markers of inflammation including a cytokine (interleukin-6 (IL-6)), acute phase reactants (C-reactive protein (CRP) and fibrinogen), and white blood cell (WBC) count are associated with maximal oxygen consumption (VO _2max) in men without coronary heart disease (CHD). Asymptomatic men (n=172, mean age 51±9.3 years) underwent measurement of VO _2max during a symptom-limited graded treadmill exercise test. Physical activity level was assessed by a standardized questionnaire. IL-6 and CRP were measured by immunoassays, fibrinogen by the Clauss method, and WBC count using a Coulter counter. IL-6 and CRP were log-transformed to reduce skewness. Multivariable regression was used to assess whether markers of inflammation were associated with VO_2max after adjustment for age, body mass index (BMI), CHD risk factors, and lifestyle variables (physical activity level, percent body fat, and alcohol intake). Mean (±SD) VO_2max was 34.5±6.1 ml/kg/min. Log IL-6 (r=-0.38, P < 0.001), log CRP (r=-0.40, P < 0.001), fibrinogen (r=-0.42, P < 0.001), and WBC count (r=-0.22, P=0.004) were each correlated with VO_{2 max}. In separate multivariable linear regression models that adjusted for age, BMI, CHD risk factors and lifestyle variables, log IL-6 (±SE = -1.66±0.63, P=0.010), log CRP (±SE=-0.99±0.33, P=0.003), fibrinogen (±SE=-1.51±0.44, P=0.001), and WBC count (±SE=-0.52±0.30, P=0.088) were each inversely associated with VO_2max. In conclusion, higher circulating levels of IL-6, CRP, and fibrinogen are independently associated with lower VO_2max in asymptomatic men.