Forest productivity depends on nutrient supply, and sustained increases in forest productivity under elevated carbon dioxide (CO2) may ultimately depend on the response of microbial communities to changes in the quantity and chemistry of plant-derived substrates, We investigated microbial responses to elevated CO2 in a warm-temperate forest under free-air CO2 enrichment for 5 years (1997–2001). The experiment was conducted on three 30 m diameter plots under ambient CO2 and three plots under elevated CO2 (200 ppm above ambient). To understand how microbial processes changed under elevated CO2, we assayed the activity of nine extracellular enzymes responsible for the decomposition of labile and recalcitrant carbon (C) substrates and the release of nitrogen (N) and phosphorus (P) from soil organic matter. Enzyme activities were measured three times per year in a surface organic horizon and in the top 15 cm of mineral soil. Initially, we found significant increases in the decomposition of labile C substrates in the mineral soil horizon under elevated CO2; this overall pattern was present but much weaker in the O horizon. Beginning in the 4th year of this study, enzyme activities in the O horizon declined under elevated CO2, whereas they continued to be stimulated in the mineral soil horizon. By year 5, the degradation of recalcitrant C substrates in mineral soils was significantly higher under elevated CO2. Although there was little direct effect of elevated CO2 on the activity of N- and P-releasing enzymes, the activity of nutrient-releasing enzymes relative to those responsible for C metabolism suggest that nutrient limitation is increasingly regulating microbial activity in the O horizon. Our results show that the metabolism of microbial communities is significantly altered by the response of primary producers to elevated CO2. We hypothesize that ecosystem responses to elevated CO2 are shifting from primary production to decomposition as a result of increasing nutrient limitation.