It is unclear if the response to positive airway pressure (PAP) treatment is different between African American (AA) and European Americans (EA). We examined whether race modifies the effects of PAP on sleep and daytime function. We assessed Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire, Psychomotor Vigilance Task and actigraphy in 185 participants with moderate-to-severe obstructive sleep apnea before and 3–4 months after PAP treatment. The participants were middle-aged (mean, 55.1 years), 83.8% men and 60.5% AA. Linear regression models were used to examine the effect of race on outcomes. The AA had smaller reductions in ESS (mean change (95% confidence interval, CI) AA, −2.30 [−3.35, −1.25] vs. EA, −4.16 [−5.48, −2.84] and frequency of awakenings (AA, −0.73 [−4.92, 3.47] vs. EA, −9.35 [−15.20, −3.51]). A race × PAP usage interaction term was added to the model to examine if the change in outcomes per 1 h increase in PAP usage differed by race. AA exhibited greater improvement in wake after sleep onset (β (95% CI) AA, −8.89 [−16.40, −1.37] vs. EA, 2.49 [−4.15, 9.12]) and frequency of awakening (β (95% CI) AA, −2.59 [−4.44, −0.75] vs. EA, 1.71 [−1.08, 4.50]). The results indicate the importance of race in evaluating outcomes following PAP treatment.