The study aimed to assess the prevalence of pain, severe pain, and pain in four or more regions associated with physical activity and sedentary behavior, as well as other associated factors in severely obese adults (Body Mass Index ≥ 35 kg/m2). Baseline data from the DieTBra Trial were analyzed. The outcome variables were pain (yes/no) and pain in four or more sites (yes/no), as identified by the Brazilian version of the Nordic Musculoskeletal Questionnaire, along with the presence of severe pain (yes/no), identified based on the Numerical Pain Rating Scale (≥8). The main independent variables were moderate to vigorous physical activity (MVPA), light physical activity, and sedentary behavior, assessed by triaxial accelerometry. The variables were analyzed using multiple hierarchical Poisson regression. In 150 individuals (men, 14.67%; and women, 85.33%), with a mean age of 39.6 ± 0.7 years, there was a high prevalence of pain (89.33%), severe pain (69.33%), and pain in four or more regions (53.33%). The associated factors were shorter MVPA time with pain (p = 0.010); arthritis/arthrosis (p = 0.007) and the use of muscle relaxants (p = 0.026) with severe pain; and economic class C (p = 0.033), and economic class D (p = 0.003), along with arthritis and arthrosis (p = 0.025) with pain in four or more sites. There were no significant associations between sedentary behavior and any of the three outcomes analyzed. These findings indicate that, in severely obese individuals, shorter MVPA time is associated with a higher prevalence of pain. Future studies on physical activity intervention may contribute to the reduction in the prevalence and severity of pain in adults with severe obesity.