Introduction: Reductions in physical activity energy expenditure (PAEE) and basal metabolic rate (BMR) have been proposed as factors that may hinder diet-induced body mass loss. Although diet-mediated changes in PAEE and BMR are subject to large inter-individual variability, research investigating the impact of sex on diet-induced modulation of PAEE and BMR is lacking. Therefore, this study examined the effect of a diet-induced energy restriction on PAEE and BMR in non-exercising individuals with overweight and obesity. Methods: Eleven women (Age: 25 ± 7 yr; BMI: 29.7 ± 4.2 kg/m2) and eight men (Age 29.6 ± 4.0 yr; BMI: 29.7 ± 4.0 kg/m2) completed a 29-day investigation. Assessment of PA (PAEE and step count), BMR, body mass, systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting blood glucose (BG) occurred on days 1, 8, 15, 22 and 29. Between day 15 and day 22, participants consumed a liquid diet formula equivalent to 50% of their total daily energy expenditure. The effects of time, sex and their interaction on all variables were assessed through a two-way mixed model ANOVA. Results: Both men and women achieved a modest 3% body mass loss at the end of the intervention week. An effect of time was detected for body mass (p<0.001), BMI (p<0.001), body fat % (p=0.001), SBP (p=0.007), DBP (p=0.033) and BG (p<0.001). There was a time and sex interaction in both males and females for body mass (p=0.002), BMI (p=0.002) and body fat % (p=0.043). Sex differences were only present for body fat % (p=0.001) and BMR (p<0.001). No main or interaction effects were present for PAEE and step count. Conclusion: A 7-day diet-induced energy restriction of 50% may be a viable short-term strategy to produce initial reductions in body mass and body fat %, and improvements in fasting blood glucose and resting blood pressure with no compensatory changes on PA.