Introduction: Chronic suppurative otitis media (CSOM) is middle ear infection, perforation and inflammation usually with purulent middle ear discharge. Different immune markers such as IgE and interferon were proved to be elevated in CSOM. Aim/Objective: The aim of the study is to evaluate of these inflammatory biomarkers (IL6, IL8 and TNF gamma) in patient of CSOM to suggest future therapy of chronic infections with inflammations. Methodology: This is a case-control study conducted in ENT ward in a tertiary care hospital in Jinnah Post Medical centre, Karachi during November 2017 to May 2018. Patients or healthy volunteers were divided into two groups as G1 (without any disease) and G2 (CSOM patients without treatment), G3 (CSOM patients treated with co-amoxicillin) and G4 (CSOM patients treated with ciprofloxacin). The serum was subjected for the quantitative measurement of IL6, IL8 and TNF Gamma by ELISA Kit method via antibody-antigen-enzyme complex formation and measured at 450 nm. Result: Study shows that IL6, IL8 and TNF gamma concentration was significantly high in G2 (positive control), G3 (ciprofloxacin) and G4 (co-amoxicillin) in contrast with G1 (negative control). Moreover, IL6 concentration was significantly low in G3 (ciprofloxacin) and G4 (co-amoxicillin) as compare to G2 (positive control). Conclusion: Elevated levels of IL6, IL8 and TNF gamma in CSOM showed alteration of immune response in chronic suppurative otitis media. Moreover, anti-inflammatory role of ciprofloxacin and co-amoxicillin in CSOM may provide additional benefit beside attenuation of infection.