Introduction: In COVID-19 patients, those with underlying disease are relatively more susceptible to respiratory viral infections and are more likely to develop severe symptoms compared to people without underlying disease. Objectives: This study aimed to evaluate the serum levels of interleukin (IL)-8 and IL-17 in patients infected with severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) and patients with underlying disease. Patients and Methods: Serum samples were collected before administration of any antiviral and/or immunosuppressive drug. Around 64 adult patients with COVID-19 and 12 adult patients with underlying disease were compared with 16 healthy subjects as controls. The cytokine levels were assessed by ELISA (enzyme-linked immunosorbent assay) method and the statistical analysis was carried out using the one-way analysis of variance (ANOVA). Results: The average levels of these cytokines in the severe group were significantly higher than those in the mild and control group (r=0.48, P<0.016); it is worth noting that patients with underlying disease also displayed a higher level of these cytokines than those with mild and control groups ( r = 0.283, P<0.049). No significant differences were observed between severe and other patients with underlying disease and also between mild and control groups. Conclusion: Our data indicate that IL-17 and IL-8 are involved in inducing and mediating proinflammatory responses and that the elevated level of these inflammatory cytokines could be the effective ground in the severity of COVID-19 and being susceptible in people with underlying disease. Thus, providing a platform of inflammatory signature cytokines in COVID-19 patients with underlying co-morbidities or without as well as in non-COVID-19 patients with underlying diseases might provide a promising solution to COVID-19 disease.