Objective: The current study aimed to evaluate the anti-inflammatory potency of combined curcumin and capsaicin against lipopolysaccharide (LPS) induced organ damage in mice. Methods: Adult male albino mice were distributed into five experimental groups for treatment with olive oil, LPS, curcumin, capsaicin and their combination, respectively, for 7 days prior to LPS induced inflammation. At the end of the experiment, blood samples were collected and used for the analysis of serum non-specific enzymes including serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin (TB), urea, creatinine and sugar, while the organ homogenates were subjected for the evaluation of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutothione S transferase (GST), nitric oxide (NO); lipid peroxidation (LPO) and it was further confirmed by histopathological study of different organs. Results and Conclusion: Curcumin, capsaicin and their combination had shown significant restoration of non-specific serum enzymes, antioxidant enzymes and attenuated inflammatory cells infiltration thereby preventing tissue/organ damage in LPS-challenged mice. However, the protective effect was found to be more when the two compounds were fed in combination. This beneficial potency of combined spice treatment is may be due to the contribution of diversified active moieties of curcumin and capsaicin in combination compared to individual molecules.