ABSTRACT Two field experiments were conducted in clay soil during the two winter seasons of 2014/2015 and 2015/2016 to study the response of lettuce plants (Lactuca sativa L.) to different sources and doses of nitrogen fertilizer. Two mineral N fertilizer sources, i.e., Ammonium Nitrate (33.5% N) and Ammonium Sulphate (20.5% N) were compared to organic manure (2.07-2.21% N) as a natural organic N source at different application doses, i.e., 60, 80 and 100 kg N/feddan (4200 m2). The experiments were carried out in a split plot design with three replicates, where three different N sources were occupied the main plots and three different N doses were randomized in sub experimental plots. Plant fresh weight, dry matter, total chlorophyll and heads yield as well as chemical composition of lettuce heads, i.e., vitamin C, nitrate, N, P and K were evaluated. The data showed that applying of mineral-N sources increased plant fresh weight, chlorophyll content and heads yield as well as N, P and K in lettuce heads compared to organic-N source. Ammonium Sulphate ranked the first in increasing lettuce yield followed by Ammonium Nitrate and lastly coming organic manure. Organic manure resulted in the highest values of dry matter and vitamin C in lettuce heads and the lowest value of nitrate in lettuce heads. The productivity of lettuce and most of chemical contents in lettuce heads were increasing with increasing application doses from 60 to 100 kg N/feddan. The moderate application dose (80 kg N/feddan) resulted in the highest values of dry matter and vitamin C in lettuce heads, and the samestatistically productivity with less nitrate content compared to the highest application dose (100 kg N/feddan).