Mille-Serdo Wildlife Reserve (Amharic: ማይል ሰርዶ የዱር አራዊት ጥበቃ) is a protected area in Ethiopia.

The reserve protects a portion of the Awash River and the surrounding desert.

[1] It is located in the Afar Depression, a desert region lying between the Red Sea and the Ethiopian Highlands.

[2] The reserve includes the lower reach of the Awash River, which originates in the Ethiopian Highlands and flows through the African Rift Valley to empty into saline lakes, including Lake Abbe, which lie immediately southeast of the reserve along the Ethiopia-Djibouti border.

[1] The reserve was created to protect the critically endangered Somali wild ass (Equus africanus somaliensis).