Cold-exposure promotes energy expenditure by inducing brown adipose tissue (BAT) thermogenesis, which over time, is also sustained by browning, the appearance, or increase, of brown-like cells into white fat depots. Identification of circulating markers reflecting BAT activity and browning is crucial to study this phenomenon and its triggers, also holding possible implications for the therapy of obesity and metabolic diseases. Using RT-qPCR, we evaluated the peripheral blood mononuclear cells (PBMC) expression profile of regulators of BAT activity (CIDEA, PRDM16), white adipocytes browning (HOXC9 and SLC27A1), and fatty acid β-oxidation (CPT1A) in 150 Siberian healthy miners living at extremely cold temperatures compared to 29 healthy subjects living in thermoneutral conditions. Anthropometric parameters, glucose, and lipid profiles were also assessed. The cold-exposed group showed significantly lower weight, BMI, hip circumference, and PBMC expression of CIDEA, but higher expression of HOXC9 and higher circulating glucose compared to controls. Within the cold-exposed group, BMI, total cholesterol, and the atherogenic coefficient were lower in individuals exposed to low temperatures for a longer time. In conclusion, human PBMC expresses the brown adipocytes marker CIDEA and the browning marker HOXC9, which, varying according to cold-exposure, possibly reflect changes in BAT activation and white fat browning. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.