Background: Musculoskeletal pain is associated with obesity; however, information on factors associated with pain in adults with obesity and severe obesity is limited. The purpose of this study was to assess the prevalence of musculoskeletal pain by site and intensity of pain and associated factors in individuals with severe obesity (body mass index ≥ 35.0 kg/m2). Methods: Baseline data from the DieTBra Trial study evaluating pain symptoms in nine body regions over the last seven days using the Nordic Questionnaire on Musculoskeletal Symptoms and Numerical Pain Scale. The variables analyzed using multiple Poisson regression with hierarchical analysis were: sociodemographic, lifestyle, food consumption, clinical, and anthropometric, and the outcome was moderate and intense pain. Results: In 150 participants, there was a high prevalence of ankle and foot pain (68.7%), lower back pain (62.7%), pain in the knees (53.3%) and upper back pain (52.0%), with a predominance of intense pain. Factors associated with pain according to specific sites were: type 2 diabetes with hand/wrist pain; sedentary time with hip pain; insomnia with pain in the hip and knee; edema in the lower limbs with pain in the lower back and ankles/feet; degree of obesity with ankle/foot pain; and percentage of total fat with ankle/foot pain. Conclusions There was a high prevalence of pain and intense pain in individuals with severe obesity and an association with clinical variables, the degree of obesity, and sedentary lifestyle.