We tested whether stressful workplace characteristics confound or moderate the association between occupational physical activity and depressive symptoms. We used data of 36,442 employed adults (16,992 women), with a mean age of 39.3 ± 12.6y, from the 2013 Brazilian National Health Survey. Depressive symptoms were assessed through the Patient Health Questionnaire-9 (cut-point: ≥10). Occupational physical activity was self-reported and classified using the cutpoint of 150 min/week and the highest quintile. Ten stressful workplace characteristics (e.g. exposure to stress, noise, violence) were also self-reported dichotomously. Logistic regression models were used considering the adjustment for potential confounders. Most of the stressful workplace characteristics were associated with elevated depressive symptoms (8/10 characteristics) and higher occupational physical activity (9/10 characteristics). Although there were no interactions in combined associations, we found that the association between occupational physical activity and depressive symptoms consistently reduced after adjusting for the cluster of positive screening for at least two stressful workplace characteristics in men [highest quintile: ORunadjusted: 1.63 (95%CI 1.22–2.17) vs ORadjusted: 1.36 (1.08–1.91); ≥150 min/week: ORunadjusted: 1.43 (1.09–1.88) vs ORadjusted: 1.25 (0.95–1.64)], and women [highest quintile: ORunadjusted: 2.15 1.73–2.66) vs ORadjusted: 1.83 (1.47–2.29); ≥150 min/week: ORunadjusted: 2.11 (1.68–2.65) vs ORadjusted: 1.80 (1.42–2.27)]. The cross-sectional design limits the causal inference. Stressful workplace characteristics did not moderate, but acted as confounders in the association between occupational physical activity and elevated depressive symptoms and should be considered in future studies.