Purpose: Aging is associated with a gradual loss of muscle mass, which some have suggested to be accelerated by short periods of muscle disuse due to medical illness. We investigated the effect of hospitalization on skeletal muscle mass in acutely ill geriatric patients with focus on the relationship between systemic inflammatory marker C-reactive protein (CRP) and changes in muscle mass, as well as the influence of resistance training upon muscle mass. Method: Unilateral leg press resistance exercise was conducted daily during the hospital period. Outcomes included changes in whole body and regional lean mass, maximal voluntary contraction of the knee extensors, leg extension power, and functional performance. Activity level was measured using ActivPAL accelerometers, and CRP levels were obtained from blood samples. Results: Sixteen subjects completed the study (eight men and eight women, age = 84.8 T 1.9 yr, mean T SE). Lean mass at the midthigh region of the trained leg increased by 2.4% T 1.1% (P G 0.05) after the intervention period. There was a negative association between changes in midthigh lean mass of the trained leg and CRP (rs = j0.53, P G 0.05). Leg extension power increased significantly in both legs (P G 0.05), with no difference observed between legs. There were no changes in maximal voluntary contraction or functional performance. Conclusion: Muscle mass is not significantly lost during short-term hospitalization of relatively high functioning and active geriatric patients although our findings are potentially affected by changes in hydration status. Resistance training during hospitalization increases skeletal muscle mass, and patients with high levels of systemic inflammation demonstrate less ability to increase or preserve muscle mass in response to resistance training during illness.