Leaf spots caused by fungal pathogens or abiotic factors can be prevalent on southern blueberries after harvest during the summer and fall, yet little is known about how they affect physiological processes that determine yield potential for the following year. In this study, we measured CO2 assimilation and leaf conductance on field-grown blueberry plants affected by Septoria leaf spot (caused by Septoria albopunctata) or by edema-like abiotic leaf blotching. Net assimilation rate (NAR) on healthy leaves varied between 6.9 and 12.4 μmol m-2 s-1 across cultivars and measurement dates. Infection by S. albopunctata had a significant negative effect on photosynthesis, with NAR decreasing exponentially as disease severity increased (R2 ≥0.726, P < 0.0001). NAR was reduced by approximately one-half at 20% disease severity, and values approached zero for leaves with >50% necrotic leaf area. There was a positive, linear correlation between NAR and leaf conductance (R2 ≥ 0.622, P < 0.0001), suggesting that the disease may have reduced photosynthesis via decreased CO2 diffusion into affected leaves. Estimates of virtual lesion size associated with infection by S. albopunctata ranged from 2.8 to 3.1, indicating that the leaf area in which photosynthesis was impaired was about three times as large as the area covered by necrosis. For leaves afflicted by edema-like damage, there also was a significant negative relationship between NAR and affected leaf area, but the scatter about the regression was more pronounced than in the NAR-disease severity relationships for S. albopunctata (R2 = 0.548, P < 0.0001). No significant correlation was observed between leaf conductance and affected area on these leaves (P = 0.145), and the virtual lesion size associated with abiotic damage was significantly smaller than that caused by S. albopunctata. Adequate carbohydrate supply during the fall is critical for optimal flower bud set in blueberry; therefore, these results document the potential for marked yield losses due to biotic and abiotic leaf spots.