Background: Physical activity (PA) has been found to be an excellent predictor of mortality beyond traditional measures in COPD. We aimed to determine the association between depression and anxiety with accelerometry-based PA in patients with COPD. Methods: We performed a cross-sectional analysis of baseline data from 148 stable patients with COPD enrolled in an ongoing, longitudinal, observational study. We measured PA (total daily step count) with a Stepwatch Activity Monitor over 7 days, depression and anxiety with the Hospital Anxiety and Depression Scales (HADSs), dyspnea with the Shortness of Breath Questionnaire, and functional capacity with the 6-min walk test. Results: Increased anxiety was associated with higher levels of PA such that for every one-point increase in the HADS-Anxiety score there was a corresponding increase of 288 step counts per day (β = 288 steps, P < .001), after adjusting for all other variables. Higher levels of depressive symptoms were associated with lower PA (β = -176 steps, P = .02) only when anxiety was in the model. The interaction term for anxiety and depression approached significance (β = 26, P = .10), suggesting that higher levels of anxiety mitigate the negative effects of depression on PA. Conclusions: The increased PA associated with anxiety in COPD is, to our knowledge, a novel finding. However, it is unclear whether anxious patients with COPD are more restless, and use increased psychomotor activity as a coping mechanism, or whether those with COPD who push themselves to be more physically active experience more anxiety symptoms. Future studies should evaluate for anxiety and PA to better inform how to improve clinical outcomes.