BACKGROUND: Studies have shown that physical activity levels can be inversely associated with high-sensitivity C-reactive protein (hs-CRP) levels. However, the amount of physical activity required to maintain normal hs-CRP levels is still a matter for speculation. OBJECTIVE: To identify the amount of physical activity necessary to discriminate the hs-CRP levels in adults. DESIGN AND SETTING: Cross-sectional study at six teaching and research institutions. METHODS: The study sample comprised 10,231 adults aged 35 to 74 years who were participants in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Receiver operating characteristic (ROC) curves were constructed to compare the amount of physical activity in two domains (leisure time and commuting) with hs-CRP levels. The sensitivity and specificity were calculated to identify the best cutoff for physical activity level that would be needed to maintain normal levels of hs-CRP (< 3 mg/l). RESULTS: The area under the ROC curve was only statistically significant for discriminating normal levels of hs-CRP according to the amount of physical activity when the two study domains were added together. The accumulated physical activity level of 200 minutes/week was the best cutoff for discriminating normal levels of hs-CRP in adults of both sex. CONCLUSIONS: Physical activity in the leisure-time and commuting domains together, of duration 200 minutes/week, was associated with normal hs-CRP values.