ABSTRACT: Polycystic ovary syndrome (PCOS) continues to be one of the most complex reproductive and endocrine disorder among women of reproductive age. Recent reports have identified close interaction of Vitamin D deficiency and oxidative stress (OS) in exacerbating the pathophysiology of PCOS. This current study aims at assessing the combine effect of MitoQ10 and Vitamin D3 on dehydroepiandrosterone (DHEA) induced PCOS. Following successful induction of PCOS using DHEA, mice were organized into five groups (n = 8) namely: Negative Control (NC), Vitamin D3 Vehicle (VDV), Vitamin D3 (VD), MitoQ10 (MQ), Vitamin D3 plus MitoQ10 (V+M) and DHEA, ethanol and distilled water, Vitamin D3, MitoQ10 and Vitamin D3 plus MitoQ10 were respectively administered for 20 consecutive days. The study also included positive control (PC) group (n = 8) in which no treatment was applied. Treatment effects were assessed using hormonal assays, biochemical assays, Real-Time PCR, western blotting and histological analysis. Combination of Vitamin D3 and MitoQ10 significantly reduced levels of estradiol, progesterone, FSH, LH, LH/FSH, SOD and MDA. The expression rate of mRNAs of 3?-HSD, Cyp19a1, Cyp11a1, StAR, Keap1, HO-1 and Nrf2 were also significantly low in V+M group. Moreover, the histomorphological inspection of ovaries from this group revealed many healthy follicles at various stages of development including few atretic follicles, pre-antral and antral follicles and many corpora lutea. The characteristics observed in this group were in many ways similar to that of the PC group. The combination of MitoQ10 and Vitamin D3 may be potential candidate to ameliorate PCOS.