Technical Abstract: High dietary calcium (Ca) in the context of a dairy food matrix has been shown to reduce obesity development and associated inflammation in diet-induced obese (DIO) rodents. The influence of Ca and dairy on these phenotypes in the context of pre-existing obesity is not known. Furthermore, interpretations have been confounded historically by differences in body weight gain among DIO animals fed dairy-based protein or high Ca. Adiposity along with associated metabolic and inflammatory outcomes were measured in DIO mice previously fattened for 12 wk on a soy protein-based obesogenic high fat diet (45% energy, 0.5% adequate Ca), then fed one of three high fat diets (n = 30/group) for an additional 8 wk: control (same as lead-in diet), high-Ca (1.5% Ca), or high-Ca + nonfat dry milk (NFDM). Mice fed high-Ca + NFDM had modestly, but significantly, attenuated weight gain compared to mice fed high-Ca or vs. controls (P < 0.001), whereas mice fed high-Ca alone had increased weight gain compared to controls (P < 0.001). Total measured adipose depot weights between groups were similar, as were white adipose tissue inflammation and macrophage infiltration markers (e.g., TNFa, IL-6, CD68 mRNAs). Mice fed high-Ca + NFDM had significantly improved glucose tolerance following a glucose tolerance test, and markedly lower liver triglycerides compared to high-Ca and control groups. Conclusions: Improved metabolic phenotypes in pre-fattened DIO mice following provision of a diet enriched with dairy-based protein and carbohydrates appeared to be driven by non-Ca components of dairy, and were observed despite minimal differences in body weight or adiposity.