Water stress decreases the quality of fruit by generating reactive oxygen species. Grafting is a technique that can improve the efficiency of crop water usage. This work was performed in order to assess the effect of different water stresses on the commercial and nutraceutical quality of a melon fruit. Cantaloupe melon plants, grown under shade houses were grafted onto a creole pumpkin rootstock and grown with different water stresses (20, 30, and 40 kPa). The grafted melon plants under 30-kPa water stress (G30) showed greater fruit firmness and increased catalase activity. The G30 fruits showed an increase in GPX activity of up to 80% over the non-grafted plants. The GSH was higher in fruits subjected to the 40-kPa water tension. The superoxide dismutase showed a 15% greater inhibition in the fruits from the non-grafted plants. At higher water tensions, the DPPH antioxidant activity decreased, while the vitamin C content increased.