A pot experiment was conducted at EL-Zafaran village, Kafr El-Sheikh Governorate, Egypt in reclaimed sandy soil  collected from Baltim city at North Nile River region, to study the effect of bio-organic fertilizer (bio-compost) and mineral nitrogen fertilizer, both applied in different rates either each alone or both in combination, on the growth, NO₃ concentration and biochemical composition of lettuce plants (Lactuca sativa L.  c.v. Alcapucci and to evaluate their effect on the soil chemical and biological properties as well. All results were evaluated after 10, 20 and 30 days from transplanting. Results revealed that bio-compost addition (100%) caused the highest values in fresh and dry weight, head diameter of lettuce plants as well as in total microbial counts. Acquired information demonstrated that the most astounding estimations of N, P and K components following 30 days recorded 4.13, 0.467 and 3.76% under 100% rice straw compost treatment compared to mineral fertilizer control (3.53, 0.353 and 3.26 % respectively),  Chemical properties of sandy soil such as available elements (N,P,K) and chemical analysis are greatly affected by addition of bio-compost. The best values (pH, EC and OM)   were recorded in treatments received 100% compost. Plants treated with 50% mineral + 50% rice straw compost  recorded the highest value of nitrogenase activity being 400.78 µmole C₂H₄ 100 g^-1 day^-1 at 10 days from sowing as compared to the other treatments, however  these values decreased to 24.96 µmole C₂H₄ 100 g^-1 dayafter 30 days. Therefore, the application of 100% rice straw compost is recommended for farmers to get higher yields of lettuce and reduce sources of ecological pollution and keep up human health.