It is unknown how changes in physical activity may affect changes in quality of life (QoL) outcomes during lifestyle interventions for severely obese adults. The purpose of this study was to examine associations in the patterns of change between objectively assessed physical activity as the independent variable and physical, mental, and obesity-specific QoL and life satisfaction as the dependent variables during a two-year lifestyle intervention. Forty-nine severely obese adults (37 women; 43.6±9.4 years; body mass index 42.1±6.0 kg/m2) participated in the study. Assessments were conducted four times using Medical Outcomes Study Short-Form 36 Health Survey (SF-36), Obesity-Related Problems (OP) scale, a single item on life satisfaction, and accelerometers. The physical component summary (PCS) score and the mental component summary (MCS) score were used as SF-36 outcomes. Associations were determined using linear regression analyses and reported as standardized coefficients (stand. coeff.). Change in physical activity was independently associated with change in PCS (stand. coeff. = 0.35, P=.033), MCS (stand. coeff. = 0.51, P=.001), OP (stand. coeff. = −0.31,  P=.018), and life satisfaction (stand. coeff. = 0.39, P=.004) after adjustment for gender, age, and change in body mass index.