Fluorosis is a major public health problem in the world, including India. The present study was undertaken to investigate the role of molybdenum (Mo) in the deposition of fluoride (F) in bone and whether copper (Cu) supplementation has any alleviating role when F and Mo are ingested together. For this purpose, four groups of rabbits were used [control (C), fluoride (F), fluoride + molybdenum (F + Mo), and fluoride + molybdenum + copper (F + Mo + Cu)] to find out the effect of these treatments on various bone-related parameters like intact parathyroid hormone (iPTH), alkaline phosphatase and Cu in serum, hydroxyproline and calcium (Ca) in urine, and minerals (F, Cu, manganese, and zinc) in femur bone ash. Bone mineral content (BMC), bone mineral density (BMD) [by dual energy X-ray absorptiometry (DXA)], and strength of femur bones were also assessed. F content in the femur was significantly higher (P < 0.01) in all experimental groups compared to control group. Mo supplementation increased F deposition in femur bone in the F + Mo group, whereas supplementation of Cu reduced F deposition in the F + Mo + Cu group compared to the F + Mo and F groups. Levels of Cu in femurs of the F + Mo and F + Mo + Cu groups were significantly higher (P < 0.05, P < 0.01, respectively) than in the C group, although serum Cu was significantly lower in the F and F + Mo than the C and F + Mo + Cu groups. Magnesium levels in the F + Mo group were significantly higher (P < 0.05) than in the F and F + Mo + Cu groups. Cu supplementation in the F + Mo + Cu group increased deposition of zinc significantly (P < 0.05) compared to the F and F + Mo groups. Serum iPTH, alkaline phosphatase, and urinary hydroxyproline and Ca were significantly higher (P < 0.01) in the F and F + Mo than in the C and F + Mo + Cu groups. However, serum iPTH and urinary hydroxyproline were higher in the F + Mo group than the F group. Alkaline phosphatase was significantly higher in the F + Mo group than the F and F + Mo + Cu groups. Levels of serum Cu in the F and F + Mo groups were lower than in the C group, though serum Cu was significantly higher in the F + Mo + Cu than in all other groups. DXA analysis of femur bone indicated that BMD in the F + Mo group was significantly higher than in the F (P < 0.05), C (P < 0.01), and F + Mo + Cu (P < 0.05) groups. However, there was no significant difference in BMC among the groups. Bone strength was significantly higher (P < 0.05) in the F + Mo group than in the C group. Results of the present study show that ingestion of Mo with F does not create secondary Cu deficiency (due to increased excretion of Cu through urine). However, Cu concentration was decreased in serum in this group (F + Mo) compared to the C and F + Mo + Cu groups. Deposition of F in femur bone was more (22%) when it was given along with Mo compared to F alone, while F deposition in femur bone was less in the F + Mo + Cu group by 80% compared to the F group. Also, deposition of F in the F + Mo + Cu group was 120% less compared to the F + Mo group. The increase in F level due to Mo addition appears to be offset by supplementation with Cu. Supplementation with Cu showed a beneficial effect on bone resorption as well as bone formation.