Purpose.-Physical inactivity is associated with disruptions in glucose metabolism and energy balance, whereas energy restriction may blunt these adverse manifestations. During hypocaloric feeding, higher-protein intake maintains lean mass which is an important component of metabolic health. This study determined whether mild energy restriction preserves glycemic control during physical inactivity and whether this preservation is more effectively achieved with a higher-protein diet.Methods.-Ten adults (24±1 year) consumed a control (64% carbohydrate, 20% fat, 16% protein) and higher-protein diet (50% carbohydrate, 20% fat, 30% protein) during two ten-day inactivity periods (>10,000→~5,000 steps/day) in a randomized cross-over design. Energy intake was decreased by ~400 kcal/d to account for reduced energy expenditure associated with inactivity. A subset of subjects (n=5) completed ten days of inactivity while consuming 35% excess of their basal energy requirements, which served as a positive control condition (overfeeding+inactivity).Results.-Daily steps were decreased from 12,154±308 to 4,275±269 steps/day (P<0.05) which was accompanied by reduced VO 2 max (−1.8±0.7 ml/kg/min, P<0.05), independent of diet conditions. No disruptions in fasting or postprandial glucose, insulin, and nonesterified fatty acids in response to 75-g of oral glucose were observed following inactivity for both diet conditions (P>0.05). Overfeeding+inactivity increased body weight, body fat, HOMA-IR, and 2-hour postprandial glucose and insulin concentrations (P<0.05), despite no changes in lipid concentrations.