Objective: This study aimed to assess whether changes in resting metabolic rate (RMR), exercise-induced energy expenditure (EIEE), and appetite following weight loss (WL) are associated with weight regain at 1 year. Methods: Thirty-six adults with obesity underwent 8 weeks of a very-low-energy diet, followed by 4 weeks of refeeding and a 1-year maintenance program. RMR, EIEE, appetite ratings, and active ghrelin, peptide YY, glucagon-like peptide-1, cholecystokinin, and insulin concentrations were measured at baseline, week 13, and 1 year. Results: A 17% WL (−20 ± 5 kg [mean ± SD]; range: −11.7 to −32.2 kg; P < 0.001) was achieved at week 13. After 1 year, weight regain was 2.5 ± 9.0 kg (not significant), ranging from −18.2 to 22.5 kg. Both fat mass and fat-free mass were reduced at week 13 (−17.9 ± 4.8 and −2.9 ± 2.7 kg, respectively; P < 0.001), while only loss of fat mass was sustained at 1 year. WL was associated with reduced RMR, EIEE, and fasting/postprandial insulin (all P < 0.001), as well as increased fasting hunger (P < 0.01) and fasting/postprandial active ghrelin (P < 0.001). There were no significant correlations between changes in RMR, EIEE, or appetite with WL and weight regain at 1 year. Conclusions: No clear evidence emerged that changes in RMR, EIEE, or appetite following WL can predict weight regain at 1 year, but larger studies are needed to confirm these results.