We investigated the contribution of NOX-2 to redox balance, mitochondrial respiration, and glycolytic compensation in lineage-negative Sca-1⁺c-Kit⁺ (SKL) bone marrow stem cells from wild-type (WT) and NOX-2 knockout (NOX2-KO) mice. Proteomic profiling identified differentially expressed proteins involved in hypoxic response, glycolysis, and oxidative stress adaptation between WT and NOX2-KO SKL cells.