Background: Differences in energy metabolism and physical activity (PA) may contribute to the long-term regulation of body weight (BW). Objective: To examine the associations between metabolic determinants, energy expenditure and objectively measured components of PA with change in BW and fat mass (FM). Design: Prospective (4 years.), case-control study in obese (n ¼ 13) and normal weight (n ¼ 15) young adults. Measurements: At baseline, we measured resting metabolic rate, substrate oxidation, movement economy (ml O 2 kg À1 min À1 ), aerobic fitness (VO 2max ), total and PA energy expenditure by doubly labelled water, and PA by accelerometry. Fat mass was measured by DXA. At follow-up we repeated our measurements of PA and FM. Results: Fat mass increased significantly (Po0.001) in both groups. Physical activity did not change between baseline and 'follow up'. Change in overall PA (counts per minute) was inversely associated with change in BW and (b ¼ À0.0124, P ¼ 0.054) and FM (b ¼ À0.008, P ¼ 0.04). Post hoc analyses suggested that this association was explained by changes in the normal weight group only (b ¼ À0.01; P ¼ 0.008; and b ¼ À0.0097; P ¼ 0.009, for BW and FM, respectively). Metabolic determinants, energy expenditure estimates and subcomponents of PA (i.e. time spent at different intensity levels) were not significantly associated with change in BW or FM. Conclusion: Our results suggest an independent association between PA and FM. However, this association may differ depending on obesity status. The gain in FM, without any change in PA, may suggest that dietary intake is the major contributor to the positive energy balance.