BackgroundIntermittent fasting (IF) is a dietary approach that is widely popular due to its effects on weight and body fat loss, but it does not appear to ensure muscle mass preservation. Incorporating high-intensity interval training (HIIT) into an individual’s routine could be an attractive and viable therapeutic option for improving body composition, lifestyle and health promotion. Problematizing the emerging situation of fighting obesity, led us to clarify gaps about IF and hypothesize that IF and HIIT in conjunction may protect against muscle mass decline without impairing nitrogen balance (NB), in addition to improving the physical fitness of women with obesity.ObjectivesTo evaluate the effects of IF alone and combined with HIIT on body composition, NB and strength and physical fitness in women with obesity.MethodsThirty-six women (BMI 34.0 ± 3.2; 32.2 ± 4.4 years) participated and were randomly distributed into three groups: (1) Intermittent fasting combined with exercise group (IF + EX); (2) Exercise group (EX); and (3) Intermittent fasting group (IF). The interventions took place over 8 weeks and all evaluations were performed pre and post-intervention. The HIIT circuit was performed 3x/week, for 25 mins/session, at 70–85% of the maximum heart rate. The intermittent fasting protocol was a 5:2 diet with two meals within 6 h on fasting days, being 25% of total energy intake, plus 18 h of complete fasting. The protocol was performed 2x/week and 5 days of ad libitum ingestion. Resting metabolic rate (RMR) was measured by indirect calorimetry, body composition by BodPod®, NB from urinary nitrogen, food consumption by food records and physical and strength performance were measured by physical tests. ANOVA two-way repeated measures mixed model was performed followed by Sidak post hoc (p < 0.05). This project was registered in ClinicalTrials.gov, NCT05237154.ResultsThere were a reduction in body weight (P = 0.012) and BMI (P = 0.031) only in the IF + EX group. There was body fat loss in the IF + EX group (−4%, P < 0.001) and in the EX group (−2.3%, P = 0.043), an increase in fat-free mass in the IF + EX group (+3.3%, P < 0.001) and also in the EX group (+2%, P = 0.043), without differences between groups and the IF group showed no changes. The NB was equilibrium in all groups. All parameters of aerobic capacity and strength improved.ConclusionCombining IF with HIIT can promote increments in fat-free mass, NB equilibrium and improve physical fitness and strength.