Introduction Infection with SARS-CoV-2 begins in the lower respiratory tract, but COVID-19 often involves the renal system, resulting in serum electrolyte imbalance. Monitoring serum electrolyte levels and parameters of liver and kidney function is essential to understand disease prognosis. Objectives This study aimed to determine the effect of imbalances in serum electrolytes and other parameters on COVID-19 severity. Material and method This retrospective study comprised 241 patients, ages 14 years and older, including 186 patients who were moderately affected and 55 who were categorized as severely affected by COVID-19. Serum electrolytes (sodium (Na+), potassium (K+), and chloride (Cl-)) and biomarkers of kidney and liver function (creatinine and alanine aminotransferase (ALT)) were measured and correlated with disease severity. This research was conducted among admitted patients of Holy Family Red Crescent Medical College Hospital designated into two groups based on retrospective hospital records. Individuals with moderate illness had evidence of lower respiratory tract infection (cough, cold, breathless, etc.) during clinical assessment or imaging (chest X-ray and computed tomography (CT) scan of the lungs) and have an oxygen saturation by pulse oximetry (SpO2) ≥ 94% on room air at sea level. The severely ill group involved individuals with SpO2 ≤94% on room air at sea level and respiratory rate ≥ 30 breaths/minute, and critically ill patients are those who needed mechanical ventilation or required intensive care unit (ICU) care. This categorization was based on the Coronavirus Disease 2019 (COVID-19) Treatment Guidelines (https://www.covid19treatmentguidelines.nih.gov/about-the-guidelines/whats-new/). Results Average Na+ and creatinine increased by 2.30 parts (95% confidence interval (CI) = 0.20, 4.81, P = 0.041) and 0.35 units (95% CI = 0.03, 0.68, P = 0.043) in severe cases compared with moderate cases. Older participants had relatively Na+ lowered to -0.06 parts (95% CI = -0.12, -0.001, P = 0.045), significant Cl- reduction by 0.09 units (95% CI = -0.14, -0.04, P = 0.001), and ALT by 0.47 units (95% CI = -0.88, -0.06, P = 0.024), whereas serum creatinine was increased by 0.01 parts (95% CI = 0.001, 0.02, P = 0.024). The creatinine and ALT of COVID-19 participants were significantly higher in males by 0.34 units and 23.2 units, respectively, compared with females. In severe COVID-19 cases compared with moderate cases, the risks of hypernatremia, elevated chloride levels, and elevated serum creatinine levels were increased by 2.83-fold (95% CI = 1.26, 6.36, P = 0.012), 5.37-fold (95% CI = 1.90, 15.3, P = 0.002), and 2.00-fold (95% CI = 1.08, 4.31, P = 0.039), respectively. Conclusion Serum electrolyte and biomarker levels can serve as good indicators of the condition and disease prognosis of patients with COVID-19. Our purpose in this study was to determine the association between serum electrolyte imbalance and disease severity. We collected data from ex post facto hospital records and did not intend to assess the mortality rate. Consequently, this study expects that the prompt diagnosis of electrolyte disparity or disturbance possibly minimizes COVID-19-related morbidity and mortality.