The Southern Red Sea region of Eritrea is one of the six main regions of Eritrea. It lies along the southern half of the Red Sea, and contains the coastal city of Assab. It borders the Northern Red Sea region, and has an area of around 27,600km².

It extends over 500km along Red Sea coast but is only around 50km wide. Forming the major part of the Danakil Desert, its major towns include Assab, Beylul, Rahaita and Thio.

It is generally considered one of the most inhospitable areas on Earth, except along the coast.