: Background: Sodium Benzoate (SB) significantly improved positive, negative, and cognitive symptoms as add on treatment in schizophrenia. Olanzapine (Ola), the most effective atypical antipsychotic drug, has been linked to hepatic steatosis, acute kidney injury, reproductive side effects and poor effect on negative symptoms in some patients. Goals: is to compare the efficacy and check the safety of long-term monotherapy with SB 0.01 mg/Kg versus Ola on male cognitive, memory, hepatic, renal and testicular functions in rat model of schizophrenia. Methods: 48 young adult male rats were divided into 6 groups; C: control; O: received Ola; SB: received SB; K: received single IP ketamine (Ket) injection; K+O: received Ola and Ket and K+SB: received SB and Ket. Ola and SB given orally for 3 or 10 weeks for behavioral or serological studies respectively. We measured activities of daily life (ADL), spatial learning and memory in radial arm water maze (RAWM), serum parameters of hepatic, renal and testicular functions. Results: Both Ola and SB significantly improved hoarding and burrowing, caused significant decrease in time to reach target (TRT), working memory errors (WME) in K+O and K+SB groups compared to K group. Ola caused significant increase in ALT, AST and creatinine and decrease in serum LH, testosterone compared to controls. SB caused significant rise in serum LH, ALT, AST and decrease in protein and albumin compared to both C and O groups. Conclusion: Both Ola and SB improved ADL, cognitive and memory functions. Although SB saved testicular and renal functions, it worsened liver function compared to Ola.