It has been previously reported that overweight and obese individuals perceive exercise as more difficult than their lean counterparts, and this difference may not be solely attributed to physiological differences. Therefore, we tested the hypothesis that individual differences in the perception of exercise difficulty during exercise, independent of concurrently measured physiological markers of exertion, are predictive of weight regain, after completion of a weight loss program. A total of 113 formerly overweight women who had previously completed a weight-loss program to achieve a normal body weight (BMI <25kg/m2) underwent a submaximal aerobic exercise task while measures of physiological and perceived exertion (rating of perceived exertion (RPE)) were recorded. Weight gain was assessed following a subsequent 1-year free-living period. Average weight regain 1 year following the intervention was 5.46 3.95kg. In regression modeling, RPE (Β = 0.21, P = 0.01), but not physiological exertion (Β = 0.02, P = 0.81), during the submaximal exercise task was positively associated with 1-year weight regain following weight loss in premenopausal women, independent of measured confounding variables. The association between RPE and weight regain suggests that perception of exercise difficulty is an important predictor of weight regain following a weight-loss intervention. © 2010 The Obesity Society.