Objective To investigate whether mitochondrial function is altered in circulating immune cells from calcium oxalate (CaOx) stone formers compared to healthy subjects. Materials and Methods Adult healthy subjects (n = 18) and CaOx stone formers (n = 12) were included in a pilot study. Data collection included demographic and clinical values from electronic medical records. Bioenergetic function was assessed in monocytes, lymphocytes, and platelets isolated from blood samples using the Seahorse XF96 Analyzer. Plasma interleukin-6 (IL-6) was measured using enzyme-linked immunosorbent assay. Results All participants were age matched (44.5 ± 3.0 years for healthy subjects vs 42.3 ± 4.8 years for CaOx stone formers, P =.6905). CaOx stone formers did not have urinary tract infection, ureteral stones, or obstructing renal stones. Monocyte mitochondrial function was decreased in CaOx stone formers compared to healthy subjects. Specifically, mitochondrial maximal respiration (P =.0011) and reserve capacity (P <.0001) were significantly lower. In contrast, lymphocyte and platelet mitochondrial function was similar between the 2 groups. The bioenergetic health index, an integrated value of mitochondrial function, was significantly lower in monocytes from CaOx stone formers compared to healthy subjects (P =.0041). Lastly, plasma IL-6 levels were significantly increased (P =.0324). Conclusion The present pilot study shows that CaOx stone formers have decreased monocyte mitochondrial function. Plasma IL-6 was also increased in this cohort. These data suggest that impaired monocyte mitochondrial function and inflammation may be linked to CaOx kidney stone formation. Further studies are needed to confirm these findings in a larger cohort of patients.