Low rates of adherence to self-management behaviors are common among patients with COPD. Health literacy and cognitive abilities may influence engagement in self-management behaviors. We sought to assess the association between health literacy and cognitive abilities with self-management behaviors in patients with COPD. We conducted an observational cohort study among American adults with COPD in New York, New York, and Chicago, Illinois. Outcomes included adherence to COPD medication, metered dose inhaler (MDI) and dry powder inhaler (DPI) technique, receipt of vaccination, and routine healthcare appointments. Health literacy was measured with the Short Test of Functional Health Literacy in Adults. Cognitive function was assessed in terms of global, fluid (working memory, processing speed, executive function) and crystallized (verbal) ability. Adequate health literacy was associated with adequate adherence to COPD medications (OR 1.46; 95% CI, 1.02–2.08), correct MDI (OR 1.66; 95% CI, 1.13–2.44) and DPI (OR 2.17; 95% CI, 1.30–3.64) technique. Fluid abilities were also associated with medication behaviors and visiting a regular healthcare provider, while crystalized abilities were not. Global cognitive abilities were associated with correct inhaler technique. No other associations were found with non-medication self-management behaviors. COPD patients with limited health literacy and deficits in fluid cognitive abilities have lower rates of adherence and poorer inhaler technique than individuals with adequate health literacy and greater fluid cognitive abilities. These findings highlight the importance of considering the health literacy level and cognitive ability when caring for and educating patients with COPD. •Limited health literacy was associated with poor adherence to COPD medications and poor inhaler technique.•Fluid cognitive abilities were associated with medication adherence and inhaler technique.•Health literacy and cognitive abilities were not associated with receipt of vaccines or routine healthcare visits.