Febrile sepsis was induced in rats by repeated s.c. injections of liveEscherichia colibacteria. Glucose utilization of different tissues was investigated in vivo by using the 2‐deoxyglucose tracer technique. In septic rats the rate of glucose utilization was increased in macrophage‐rich tissues, including the liver (2.7‐fold), spleen (2.4‐fold), and ileum (1.6‐fold), compared with tissues from time‐matched nonseptic animals. A smaller increase in glucose utilization was evident in the abdominal muscle (1.3‐fold) and in the white portion of the quadriceps muscle (1.3‐fold). Changes were not significant in nine other tissues, including the brain. We postulate that in sepsis the mononuclear phagocyte system may be responsible for most of the increment of glucose utilization, and the latter provides metabolic support for the increased antibacterial activity of these cells.—Meszaros, K.; Lang, C. H.; Bagby, G. J.; Spitzer, J. J. In vivo glucose utilization by individual tissues during nonlethal hypermetabolic sepsis.FASEB J.2: 3083‐3086; 1988.