The purpose of this study was to examine the subject and combined associations of cardiorespiratory fitness (fitness) and body mass index (BMI) with the risk of sudden cardiac death (SCD) in middle-aged men. This prospective study was based on a population sample of 2,357 men aged 42 to 60 years, who were followed up in the Kuopio Ischemic Heart Disease cohort study. Fitness was directly measured by peak oxygen uptake (VO2peak) during progressive exercise testing to volitional fatigue. Participants were divided into 4 groups (fit-normal weight, unfit-normal weight, fit-overweight/obese, and unfit-overweight/obese) based on the median values of fitness and BMI. A total of 253 (10.7%) SCDs occurred during an average follow-up of 22 years. After adjusting for potential confounders, the hazard ratio (HR) and 95% confidence interval (CI) for SCD was 1.80 (95% CI 1.21 to 2.68) for BMI ≥30.0 kg/m2 versus normal weight cohort, that is, BMI corresponding to 18.5 to 24.9 kg/m2. However, these associations were no longer statistically significant after adjusting for VO2peak (1.49, 95% CI 0.98 to 2.24). Compared with the lower levels of fitness, upper levels of fitness had a 39% lower risk of SCD (HR 0.61, 95% CI 0.40 to 0.92) after adjusting for potential confounders, including BMI. In the combined associations of fitness and BMI with the risk of SCD, unfit-overweight/obese men had 1.80 times (95% CI 1.06 to 3.06) increased risk of SCD, but fit-overweight/obese men were not at increased risk of SCD (HR 1.22, 95% CI 0.66 to 2.25) as compared with their fit-normal weight counterparts. In conclusion, both overweight/obesity and fitness were independently associated with the risk of SCD; however, fitness appears to attenuate the risk of SCD in overweight/obese men, suggesting that improving fitness may reduce the risk of SCD in this population.