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Aim: To compare the efficacy of two popular weight loss approaches on weight loss, body composition, and markers of health in sedentary obese women. Methods: In total, 51 sedentary women (age 34.5 ± 7.7 yrs.; weight 90.0 ± 14.5 kg; BMI 34.0 ± 5.1 kg/m2; 46.5 ± 7.0% fat) were matched and randomized to participate in the Weight Watchers® Momentum™ (WW) or Curves® (CV) Fitness and Weight Management program for 16 weeks. Participants in the WW group (n = 27) were provided a point-based diet program, received weekly progress checks and counseling, and were encouraged to exercise. Participants in the CV group (n = 24) followed a menu-based higher protein/low-fat diet (1200 kcal/d) for 1 week; 1500 kcal/d diet for 3 weeks; and 2000–2500 kcals/d for 2 weeks that was repeated three times (except the last segment) while participating in a supervised circuit-style resistance training program (3 d/wk). A general linear model (GLM) with repeated measures was used to analyze data and are presented as mean changes from baseline (mean [UL, LL]). Results: Supervised CV training resulted in greater amounts of vigorous and total physical activity. After 16 weeks, both groups lost weight (WW −6.1 [−7.8, −4.6], CV −4.9 [−6.2, −3.2] kg, p = 0.264). Participants in the CV group observed greater reductions in fat mass (WW −2.9 [−6.7, −0.2], CV −6.4 [−9.2, −3.6] kg, p = 0.081) and increases in lean mass (WW −2.5 [−4.3, −0.7], CV 1.3 [−0.6, 3.2] kg, p = 0.005) resulting in more favorable changes in percent body fat (WW −1.4 [−4.1, 1.2], CV −4.7 [−7.5, −1.8]%, p = 0.098). Both groups observed improvements in peak aerobic capacity and muscular endurance, although bench press lifting volume was greater in the CV group. Those in the CV group experienced a greater increase in HDLc and reduction in the CHL–HDLc ratio and triglycerides. Conclusion: Both interventions promoted weight loss and improvements in fitness and markers of health. The CV program, which included supervised resistance training and higher protein diet menus, promoted greater fat loss, increases in lean mass, and improvements in percent body fat and blood lipids. Trial Registration: clinicaltrials.gov, #NCT04372771, registered retrospectively 1 May 2020.