This work studied the effect of Saccharomyces cerevisiae (SC) supplementation on the metabolic, hormonal and reproductive efficiency of Farafra ewes in arid subtropical regions. Eighteen ewes were assigned randomly into three equal groups (6 ewes each). The treatments were C, T1, and T2, representing dietary supplementation of SC at 0, 1, and 1.5 g/h/d, respectively. Blood samples were collected from the jugular vein and the biochemical parameters were measured monthly during the experiment. The results showed non-significant effect in total protein, albumin, globulin, AST, ALT, ALP, urea-N, creatinine, total cholesterol, tri-glycerides, T3, and T4 among treatment. Whereas the concentrations of glucose increased (P<0.05) significantly in SC groups than control. The elevated conception rate was recorded for SC-treated ewes (100%) compared with (66.67%) extent of control. Also, SC significantly (P≤0.05) improved reproductive ability, lambs born per ewes joined and lambs born or weaned per ewe lambed. The presented results concluded that SC could enhance metabolic status and reproductive efficiency of Farafra ewes in arid subtropical regions.