Rheumatoid arthritis (RA) is accompanied by increased resting energy expenditure (REE) and decreased fat-free mass (FFM). This is referred to as rheumatoid cachexia and is attributed to high levels of tumour necrosis factor-alpha (TNF-alpha). This study aimed to investigate the effects of anti-TNF-alpha therapy on REE, body composition, physical activity and protein intake in RA patients. Twenty RA patients [50% female; age: (mean +/- s.d.) 61.1 +/- 6.8 yrs; body mass index (BMI): 28.3 +/- 3.7 kg/m2] and 12 age-sex-BMI-matched healthy controls were assessed. REE (indirect calorimetry), body composition (bioelectrical impedance), the International Physical Activity Questionnaire (IPAQ), diet, Health Assessment Questionnaire (HAQ), disease activity [disease activity score 28 (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein] and serum TNF-alpha were measured before (Baseline) as well as 2 weeks (Time-1) and 12 weeks (Time-2) after initiation of anti-TNF-alpha treatment. Controls were only assessed at Baseline. RA patients had significantly higher REE than controls at Baseline (1799.4 +/- 292.0 vs 1502.9 +/- 114.5 kcal/day, P = 0.002). Within the RA group, REE increased significantly between Time-1 and Time-2 (P = 0.001) but not between Baseline and Time-2. Sustained significant increases were observed in IPAQ (P = 0.001) and protein intake (P = 0.001). There were no significant changes in FFM or body fat. ESR (P = 0.002), DAS28 (P < 0.001), HAQ (P < 0.001) and TNF-alpha (P = 0.024) improved significantly. Physical activity (P = 0.001) and protein intake (P = 0.024) were significant between-subject factors for the elevation of REE. After 12 weeks of anti-TNF-alpha therapy, there were significant improvements in disease activity and physical function, as well as physical activity and protein intake, but no significant changes in REE or FFM. There is a need for longer-term studies in this field.