Rationale: Comorbidity is a significant driver of health status and healthcare utilization in chronic obstructive pulmonary disease (COPD). Obstructive sleep apnea (OSA) portends poorer outcomes, whereas obesity is protective. Objectives: We describe the prevalence and influence of these comorbidities on COPD readmissions. Methods: We collated discharge records for COPD exacerbations spanning 2010-2016 from the Nationwide Readmissions Database using Medicare's Hospital Readmissions Reduction Program criteria, with OSA-COPD overlap identified by concomitant diagnosis code for OSA. We used mixed-effects logistic regression to predict readmission odds. A cross-sectional mediation analysis was performed to evaluate the extent that OSA attenuated obesity's impact on readmission. Results: Of 1,662,983 qualifying COPD discharges, 19.1% carried a diagnosis of obesity and 12.9% had OSA, with both diagnoses present in 7.8%. In unadjusted analyses, obesity (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.03-1.05; P < 0.001) and OSA (OR, 1.11; 95% CI, 1.10-1.13; P < 0.001) had increased readmission odds. In models adjusted for patient and hospital characteristics, 71% of readmission risk from obesity was attributable to OSA. When additionally adjusted for Charlson Comorbidity Index, we found that OSA remained a significant risk factor (OR, 1.05; 95% CI, 1.03-1.06; P < 0.001), whereas obesity remained protective (OR, 0.96; 95% CI, 0.94-0.97; P < 0.001) even after accounting for OSA. Conclusions: A significant proportion of patients with COPD suffer comorbid OSA and obesity with resultant readmission risk. Interestingly, obesity's protective effect attenuates readmission odds from OSA. Taken together, OSA and aggregate comorbidity influence readmissions in patients with COPD. Testing for and treating OSA-COPD overlap may provide a mechanism to reduce avoidable readmissions.