Background: Neonatal mortality and morbidity are the greatest challenges in the current health care scenario. Majority of newborns die because mothers fail to identify danger signs of illness, and inappropriate/delayed care seeking. The most common identified newborn danger signs are fever, lethargy, inability to feed, low temperature, fast breathing, persistent vomiting, convulsions, pus draining/bleeding from umbilical area, lack of consciousness, yellow palm/sole/eye and eye discharge/redness. Objective was to assess the awareness level and factors associated towards neonatal danger sign among mothers who attend public health institutions of Mekelle City, Tigray, Ethiopia, 2015.