Coronavirus disease 2019 (COVID-19) is a severe and infectious respiratory condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). This case-control study aimed to evaluate serum levels of various immunological markers in patients with COVID-19 compared to those with bacterial pneumonia and a healthy control group. Serum samples were collected from adult participants across various COVID-19 isolation centers, including Kassala State and Ahmed Gasim Hospital, between April and June 2021. The study included 70 patients diagnosed with COVID-19, 30 with bacterial pneumonia, and 50 healthy controls. Serum levels of C-reactive protein (CRP), complement components C3 and C4, and cytokines IL-8, IL-10, IL-12, TNF-α, and IFN-γ were measured using standard reagent kits. Serum level of CRP was significantly elevated in both bacterial pneumonia and COVID-19 but significantly higher among patients with bacterial pneumonia. C3 and C4 were also increased in both patient groups, with C3 significantly higher in bacterial pneumonia. IL-8, IL-10, IL-12, TNF-α, and IFN-γ were significantly increased in bacterial pneumonia and SARS-Cov-2 compared to healthy controls. However, IFN-γ was significantly increased among patients with COVID-19 than patients with bacterial pneumonia. This study highlights the potential significant impact of COVID-19 on the immunological biomarkers investigated.