Energy-restricted high-protein diets (HPDs) have shown favorable results for body weight (BW) management, yet studies differ in their outcomes depending on the dietary protein content. Our objective was to determine the effects of dietary protein content on BW loss-related variables during a 6-mo energy restriction with the use of diets containing protein at the level of requirement [normal-protein diet (NPD), 0.8 g . kg BW(-1) (.) d(-1)] and above (HPD, 1.2 g . kg BW(-1) (.) d(-1)). In overweight and obese participants (24 men and 48 women), BW, body composition, and metabolic responses were assessed before and after subsequent energy intakes of 100, 33, and 67% of the original individual daily energy requirements. Protein intake was consistent in the NPD (0.8 +/- 0.3 g . kg BW(-1) (.) d(-1)) and HPD (1.2 +/- 0.3 g . kg BW(-1) (.) d(-1)) groups throughout the study (P < 0.001). BMI and body fat mass similarly decreased in the NPD and HPD groups (P < 0.01). Fat free mass (FFM), resting energy expenditure (REE) compared with predicted REE, and diastolic blood pressure (DBP) changed favorably with the HPD compared with the NPD group after BW loss (P < 0.05). A NPD of 0.8 g . kg BW(-1) (.) d(-1) is sufficient for BW management, whereas a HPD of 1.2 g . kg BW(-1) (.) d(-1) is necessary for preservation of REE and a stronger initial sparing effect of FFM and lowering of DBP.