BACKGROUND: Pain may interfere with daily functioning in obese persons and also with outcomes during weight loss. We examined the relationship between pain and (1) interference with daily functioning (DFi) and (2) outcomes in an obese treatment-seeking population. METHOD: Participants were 386 patients entering a residential weight loss program (body mass index, 40.7 +/- 10.12 kg/m(2)). We examined the relationships of demographic factors, pain types, and emotional status with both baseline DFi and short-term weight loss. RESULTS: Regression analysis showed that overall, total pain scores significantly predicted DFi even after controlling for other confounders (p < .05). Leg pain, joint pain, and headache predicted DFi (p's < .05) among women. Among both men and women, depression severity predicted DFi (p's < .01). For the entire sample, there was an inverse bivariate relationship between total pain score and weight loss (p < .001). Joint pain and depression (among women) and age and depression (among men) predicted reduced weight loss (p's < .05). CONCLUSION: These results highlight the value of assessing both pain and emotional status for individuals undergoing weight loss treatment since these may interfere recommendations to increase activity.