The influence of water deficit stress on the leaf characteristic and antioxidant profile of three red lettuce varieties (Lactuca sativa L.), a commonly grown salad vegetable in the Cordillera region, was studied. The leaf area, leaf length and leaf width of the lettuce plants were reduced by medium water stress (MW) and low water stress (LW). However, significant increases in total phenolics (TP) and ascorbic acid (AA) were observed in LW-treated plants. This resulted in a 13% increase in total antioxidant capacity in Red Rapids and 8% increase for both Lollo Rosa and Falbala. Total anthocyanins, however, was not influenced by water stress imposition. Moreover, the enzymatic antioxidants (i.e., superoxide dismutase, ascorbate peroxidase and catalase) increased significantly in lettuce treated with MW and LW. Red Rapids showed the highest increase in enzymatic activity while the deep red varieties Lollo Rosa and Falbala exhibited higher increases in terms of TP and AA. This research indicates that controlled water deficit can increase TP, AA and enzymatic contents in red lettuce resulting in a higher valued crop with higher antioxidant content.