Quinoa (Chenopodium quinoa Willd), recently introduced to Egypt, is a promising plant with its ability to grow in various stress conditions, and its importance in human nutrition. A potential constraint for quinoa production is downy mildew disease (Peronospora farinose f.sp. chenopodii Byford), which recorded for the first time in Egypt during 2015. Four quinoa cvs. (white Egyptian, American, Rainbow, Black) were cultivated under Middle Egypt climate at two different locations: Fayoum (Aboxa, Ibshawai center), and Bani-Sweif (Sids Research Station) governorates, Egypt during 2015/16 and 2016/17 growing seasons. Each cv. was cultivated in six plots (12 m2 area) /location, which contains 200 plant /cv. per plot. Half of the experimental plots were treated with metalaxyl and mancozeb fungicides controlling the disease. Disease incidence and severity of downy mildew (using three leaves method and percentage scales) were assessed four times yearly with 21 days interval, which began at 28 days old. Black cv.the most susceptible one was totally infected being 100 and 93% disease incidence at Bani-Sweif and Fayoum, respectively followed by Egyptian and American cvs., being 80 and 54% disease incidence at Bani-Sweif and 71 and 49 disease incidence at Fayoum, respectively. While, Rainbow cv. wasthe lowest susceptible one, being 38 and 29 disease incidence at Bani-Sweif and Fayoum, respectively. The severity of the disease was in the same trend of disease incidence. Seed yield loss caused by downy mildew disease infection ranged from 95% in black cv. to 87% in rainbow one. Fayoum climate condition is higher significant unfavorable conditions than Bani-Sweif one for downy mildew dispersal for the evaluated cvs.. A further work must be performed for the disease management.