Using a 2 x 2 factorial design, we investigated the combined impact of protein deficiency (PD) and gastrointestinal nematode infection during late pregnancy and lactation on resting metabolic rate (RMR), body composition and bone mineralization, neonatal growth, and the regulatory hormones [corticosterone, leptin, and insulin-like growth factor-1 (IGF-1)] and proinflammatory cytokines [interleukin (IL)-1 beta and IL-6] that may drive these processes. Pregnant CD1 mice, fed either a protein-sufficient (PS; 24%) or protein-deficient (PD; 6%) isocaloric diet, were infected 4 times with either 0 (sham) or 100 Heligmosomoides bakeri larvae beginning on d 14 of pregnancy. Dams were killed on d 20 postpartum and pups on d 2, 7, 14, and 21. Diet and infection had largely independent effects. The PD diet elevated corticosterone and upregulated leptin concentration in maternal serum, which was associated with reduced food intake leading to lower body mass, RMR, and body temperature. Infection reduced food intake but elevated maternal serum IL-1 beta and IL-6 and did not affect corticosterone, leptin, RMR, or body temperature. The PD diet decreased maternal bone area and bone mineral content. Infection lowered maternal bone mineral density, consistent with elevated IL-1 beta and IL-6. The elevated serum IL-1 beta and lower IGF-1 in pups of PD dams and lower serum leptin and IGF-1 in pups of infected dams were both consistent with the lower pup body mass and shorter crown-rump length. This mouse model provides a novel framework to study the impact of diet and nematode infection on bone.