Background: Osteoporosis (OP) is a prevalent degenerative bone disease among patients receiving selective serotonin reuptake inhibitors as fluvoxamine maleate (FM). Collagen hydrolysate (CH) is a nutritional component that has antiresorptive effect. Aim of Work: Evaluate the possible protective effect of CH against FM-induced OP in adult male albino rats. Material and Methods: Thirty six rats were divided into 4 groups; group I (control), group II (OP group): injected with FM daily for 4 weeks, group III (CH group): received FM concomitant with oral CH for 4 weeks, group IV (recovery group]: received only FM for 4 weeks & were left without taking any drugs for another 4 weeks. Total serum alkaline phosphatase (ALP) and calcium (ca +2 ) were measured. Bone specimens from the right femurs and first lumbar vertebrae were processed for H&E stain, Mallory's trichrome stain and immunohistochemical staining for osteopontin (OPN) and proliferating cell nuclear antigen (PCNA). This was followed by morphometric & statistical analysis. Results: Both groups II & IV showed significant elevation in ALP & reduction in Ca +2 compared to control. Bone sections revealed evident histological changes; osteocytes with pyknotic nuclei inside widened lacuna, widened haversian canals. Bone matrix showed fain areas, cavitations & multiple resorption cavities with osteoclasts. There was significant reduction in the mean thickness of compact bone, the mean area of trabecular bone, area % of OPN & mean number of PCNA +ve cells compared to control. Group III exhibited significant reduction in ALP & elevation in Ca +2 . The bone showed preserved histological architecture almost as the control. There was significant increase in the mean thickness of compact bone, the mean area of trabecular bone, area % of OPN & mean number of PCNA +ve cells compared to groups II & IV. Conclusion: CH has a potential osteoprotective effect against FM-induced osteoporosis.