Introduction: Chronic use of fluoxetine for treatment of major depresive disorder is in correlation with increased risk of bone fractures. Osteoblasts are cells that build up bone matrix, ie. they promote growth, development, and regeneration of bone tissue. Bone morphogenetic proteins promote proliferation and differentiation of osteoblasts. This research explores the effect of fluoxetine on osteoblasts, and cummulative effect of fluoxetine and bone morphogenetic protein on osteoblasts. Methods: Preosteoblast cells MC3T3-E1 were seeded on three cell culture plates and treated with bone morphogenetic proteins in two concentration levels, fluoxetine, and combination of bone morphogenetic protein and fluoxetine. From the first plate, RNA was isolated to conduct analysis of expression of selected diferentiation markers of osteoblasts via real-time polymerase chain reaction. Second plate was stained for alkaline phosphatase, and the third one was stained by von Kossa method. Results of staining were photographed, and expression of alkaline phosphatase and mineralization was determined via computer analysis of photographs. Results: Bone morphogenetic proteins 2 and 6 in both concentration levels caused significant increase of expression of all inquired parameters. Fluoxetine did not show significant impact on inquired parameters. Combination of fluoxetine and bone morphogenetic protein showed positive effect on differentiation of osteoblasts, but this effect was significantly weaker than the effect of bone morphogenetic proteins alone. Conclusion: Fluoxetine likely has inhibitory impact on signalization pathways of bone morphogenetic proteins, whereby indirectly inhibits regeneration of bone fractures and microfractures.