Blueberries (Vaccinium corymbosum L.) are cultivated worldwide and represent an important asset for the Portuguese economy. Pathogen infection and water deficiency are known to affect crops productivity worldwide, thus limiting plant yield or fruit quality. Diaporthe is a cosmopolitan genus comprising plant pathogens and endophytes, that may switch their behavior to a pathogenic phase when the host is under environmental stress (e.g., drought, precipitation). Given the scarce physiological studies on blueberry plant- pathogen interactions, in this study we aimed to evaluate the effect of Diaporthe amygdali and D. eres on 9-month-old clonal blueberries under two different water scenarios: well-watered (WW) and water deficit (WD). Morphological (lesion length) and physiological parameters (water status, leaf gas exchange, photosynthetic pigments, proline, phenolic compounds, flavonoids, starch, total soluble sugars, and lipid peroxidation) were assessed. Our results suggest that the irrigation regime applied was not sufficient to cause severe stress to plants. Under WW conditions, plants inoculated with D. eres may have used malondialdehyde content (MDA) as a signaling molecule. Although D. amygdali has caused plant mortality, this study shows that under WW conditions, plants manage to deal with pathogen attack, maintaining their physiological performance. This study also demonstrates that the interaction between fungal pathogens and water limitation seems to stimulate plant defense, through the accumulation of proline. Our findings offer crucial insights to understand how blueberry plants cope with infection by species of Diaporthe, and how plants can adapt to climate changes in the Mediterranean area (e.g., water scarcity).