Disturbances such as fire, hurricanes, and herbivory often result in the net release of CO2 from forests to the atmosphere, but the magnitude of carbon (C) loss is poorly quantified and difficult to predict. Here, we investigate the carbon balance of an oak/pine forest in the New Jersey Pine Barrens using the Canopy Conductance Constrained Carbon Assimilation (4C-A) model. The 4C-A model utilizes whole-tree sap-flux and leaf-level photosynthetic gas exchange measurements at distinct canopy levels to estimate canopy assimilation. After model parameterization, sensitivity analyses, and evaluation against eddy flux measurements made in 2006, the model was used to predict C assimilation for an undisturbed year in 2005, and in 2007 when the stand was completely defoliated for 2–3 weeks during an infestation of gypsy moths (Lymantria dispar L.). Following defoliation, only 50% of the foliage reemerged in a second flush. In 2007, canopy net assimilation (AnC), as modeled with the 4C-A, was reduced to approximately 75% of AnC in 2006 (940 vs. 1240 g C m−2 a−1). Overall, net primary production (NPP) in 2007 was approximately 240 g C m−2 a−1 (vs. 250 g C m−2 a−1 in 2006), with 60% of NPP allocated to foliage production, a short-term carbon pool. Woody biomass accumulation, a long-term carbon pool, was reduced by 20% compared with the previous year (72 vs. 57 g C m−2 a−1 in 2006 and 2007, respectively). The overall impact of the defoliation spanned 21% of upland forests (320 km2) in the New Jersey Pine Barrens, representing a significant amount of overall C not being taken up from the atmosphere by the forest, thus not accumulated in the biosphere.