To investigate whether whole-body cryotherapy (WBC) enhances weight loss, brown adipose tissue (BAT) activation, and metabolic outcomes during obesity management.

Nineteen adults with obesity were assigned to a 12-month lifestyle-based obesity management intervention with 28 WBC sessions (−110°C, 3–4 min, ~2 × week) over the first 5 months (CRYO, n = 10) or the intervention without WBC (CON, n = 9). The primary outcome was weight loss (5 and 12 months). Secondary outcomes included BAT glucose uptake and whole-body energy expenditure during cold stimulation (5 months), clinical parameters, subcutaneous adipose tissue transcriptomics, and skeletal muscle proteomics (5 and 12 months).

Weight loss in the CRYO group was 11.9% at 5 months and 9.9% at 12 months, compared to 11.5% and 8.0% in the CON group (p ≥ 0.54 for between-group differences). No significant between-group differences appeared in BAT glucose uptake, energy expenditure, adipose tissue transcriptomics, or skeletal muscle proteomics changes. However, at 5 months, the CRYO group showed greater reductions in fasting glucose (0.41 mmol/L, p = 0.026) and LDL cholesterol (0.44 mmol/L, p = 0.034).

WBC did not significantly enhance weight loss, activate BAT, or alter most metabolic responses during conventional obesity management. Further research is needed to confirm whether WBC benefits glucose and cholesterol metabolism.