Background/Objective Exercise and lifestyle interventions have been shown to reduce hepatic fat (HF) and adiposity in youth. However, the interindividual response in HF after a lifestyle intervention with or without exercise in children is unknown. The aim of the present study was to compare interindividual variability for HF, adiposity, gamma-glutamyl transferase (GGT), and the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT) in children with overweight/obesity participating in a 22-week lifestyle intervention with (intensive intervention) or without exercise (control intervention). Methods Data from 102 children (9-12 years, 55% girls) with overweight/obesity participating in the EFIGRO randomized controlled trial were analyzed. Percentage HF (magnetic resonance imaging), weight, body and fat mass index (BMI and FMI), GGT, AST/ALT, cardiorespiratory fitness (CRF, 20 meters shuttle run test) were assessed before and after the intervention by the same trained researchers. The control intervention consisted in 11 sessions of a family-based lifestyle and psycho-educational program. The intensive intervention included the control intervention plus supervised exercise (3 sessions/week). Results The prevalence of responders for HF (54% vs. 34%), weight (27% vs. 11%), BMI (71% vs. 47%), FMI (90% vs. 60%), and GGT (69% vs. 39%) was higher in the intensive than in the control group (Ps < 0.05). Responders for weight (16 +/- 3 vs. 6 +/- 2 laps) and BMI (11 +/- 2 vs. 3 +/- 4 laps) improved more CRF levels than non-responders (Ps < 0.05). Conclusions The addition of exercise to a lifestyle intervention may increase the responder rates for HF, adiposity, and GGT in children with overweight/obesity. Improvements in CRF may explain differences between weight and BMI responders and non-responders. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT02258126.