SummaryWe found that a recessive mutation, shmt1‐1, causes aberrant regulation of cell death resulting in chlorotic and necrotic lesion formation under a variety of environmental conditions. Salicylic acid‐inducible genes and genes involved in H2O2 detoxification were expressed constitutively in shmt1‐1 plants in direct correlation with the severity of the lesions. The shmt1‐1 mutants were more susceptible than control plants to infection with biotrophic and necrotrophic pathogens, developing severe infection symptoms in a high percentage of infected leaves. In addition, mutants carrying shmt1‐1 or a loss‐of‐function shmt1‐2 allele, were smaller and showed a greater loss of chlorophyll and greater accumulation of H2O2 than wild‐type plants when subjected to salt stress. SHMT1 was map‐based cloned and found to encode a serine hydroxymetyltransferase (SHMT1) involved in the photorespiratory pathway. Our results indicate that this enzymatic activity plays a critical role in controlling the cell damage provoked by abiotic stresses such as high light and salt and in restricting pathogen‐induced cell death, supporting the notion that photorespiration forms part of the dissipatory mechanisms of plants to minimize production of reactive oxygen species (ROS) at the chloroplast and to mitigate oxidative damage. Moreover, results shown here indicate that whereas production of ROS is an essential component of the hypersensitive defense response, the excessive accumulation of these toxic compounds impairs cell death containment and counteracts the effectiveness of the plant defenses to restrict pathogen infection.