Abstract An often debilitating autoimmune disease involving multiple immune cell types and tissues, Systemic Lupus Erythematosus (SLE) afflicts nearly 3 in a 1000 people, an estimated 9.7 million in the United States. Murine models of lupus are essential for the study of disease progression, prevention, and treatment of SLE, with B6.Sle1.Sle2.Sle3 triple congenic (TC) and NZB X NZW F1 hybrid (NZB/W) being two murine models commonly used for these purposes. While these murine models show similar disease symptomology, they exhibit immune cell subsets that differ metabolically. CD4+ T cells from TC mice show increased glycolysis and phosphorylation (OXPHOS) function, however CD4+ T cells from NZB/W mice demonstrate similar activity of OXPHOS and glycolysis compared to control B6 mice. B cells from both strains present similar elevated metabolism. Further, CD4+ T cell and B cell populations from these two strains display differential metabolic modulation during treatment with the same metabolic inhibitors. This contrasts with a similar therapeutic efficiency of a treatment inhibiting glycolysis with 2DG and mitochondrial respiration with metformin in both murine models of lupus. This implies metabolic inhibitors may have therapeutic efficiency across cell-specific differences in metabolic defects.