The current investigation was planned to apply some biotic and abiotic treatments singlely and/or combined to control bacterial soft rot diseases of lettuce under field conditions in Qaha region, Qalyubia Governorate, Egypt. The application of resistance inducers (jasmonic acid and salicylic acid), antibiotics (norfloxacin and tetracycline) and bio-agents (isolates of B. subtilis and Ps. fluorescens) significantly reduced the disease severity as a single treatment compared to the control treatment. Obtained results indicated that resistance inducers appeared to be most effective against bacterial soft rot disease of lettuce compared with other treatments, while antibiotics were less effective at controlling the disease. However, the interaction between bio-agents as soil drench treatment, antibiotics, or resistance inducers as foliar treatment significantly reduced the severity of lettuce bacterial soft rot disease compared with the control treatment. Furthermore, the interaction between disease severity was more reducted with interaction treatments between Ps. fluorescens isolate rather than interact with treatments between B. subtilis isolate and other treatments. However, the interaction between the isolate of Ps. fluorescens as bio-agent treatment or norfloxacin as antibiotic or salicylic acid as a plant resistance inducer, were the most effective methods to control the disease compared with other treatments. Meanwhile, the interaction between resistance inducers and antibiotics as foliar treatments were significantly reduced from the severity of lettuce bacterial soft rot disease compared with the control treatment. Disease severity was more reduced with the application of interaction between norfloxacin and resistance inducers than the interaction between tetracycline and resistance inducers. Meanwhile, the severity of the disease decreased more with the application of interaction between salicylic acid and antibiotics than the interaction between jasmonic acid and antibiotics. Generally, all combination treatments were more efficient than single treatments alone to significantly manage the spread and the infection of the disease compared to the untreated control.