Background: Protein malnutrition is prevalent in developing countries. Gestational and neonatal malnutrition were considered to contribute to the development of chronic diseases in adulthood. The aim of the present work was to investigate the influence of prenatal protein malnutrition on embryo -fetal toxic effects of the commonly used antidepressant drug Fluoxetine. Methods: The pregnant rats were divided into two sets: normally fed and protein malnourished. Each set was sub- divided into five groups of 10-14 animals each. Starting from 1st day of pregnancy, animals were fed with standard diet (20% casein). Animals specified for protein malnutrition were switched to protein deficient diet (8%casein) from the 7th day of gestation throughout the end of pregnancy. Fluoxetine hydrochloride was administrated orally in the dose levels 2mg and 8mg /kg/day from day 7 to 14 and from day 15 to 20 of gestation. At the 20^th day of gestation the outcome of pregnancy was examined immediately for viability and fetal growth parameters, placental weight as well as fetal external anomalies. Hb, RBCs count, total and differential WBCs and platelets counts were estimated. Fetuses from each group were subjected to skeletal examinations using the Alcian blue and Alizarin red technique.   Result:The results showed that prenatal protein malnutrition and administration of Fluoxetine in the high used dose level 8mg /kg were found to cause significant decrease in fetal growth parameters, and placental weights increase in resorption of fetuses  multiple hematomas. Blood examination of protein malnourished fetuses and groups treated with fluoxetine revealed significant decrease in Hb level; RBCs count & platelets, however, total the leucocytic count was increase. The incidence of skeletal abnormalities was more obvious when fluoxetine was administrated during embryogenesis period.