Background: Chronic systemic diseases (CSD) and cancer are closely related to the clinical course, severity and mortality of COVID-19 due to the immunosuppressive conditions caused by these diseases. The purpose of this study was to investigate the differences between the effects of cancer and CSD on the clinical and laboratory parameters of patients with COVID-19. Methods: The study included patients who received inpatient treatment with the diagnosis of COVID-19 at Ondokuz Mayıs University between 16 March, 2020, and 1 December, 2020. The participants were divided into four groups as follows: those without comorbidities (Group 1), those with only CSD (Group 2), those with only cancer (Group 3), and those with both CSD and cancer (Group 4). Comparative statistical evaluation was performed in terms of clinical symptoms, biochemical parameters, admission to intensive care and survival. Results: In total, 750 patients were included: 242 patients in Group 1, 442 in Group 2, 27 in Group 3, and 39 in Group 4. The mean age of the patients was 57.1 ± 9.4 years, and 53.7% were male. Patients of Group 1 were significantly different from those of the other groups in terms of age, requirement for intensive care and intubation, complications, survival, white blood cell and lymphocyte count, neutrophil/lymphocyte ratio and levels of haemoglobin, lactic acid dehydrogenase, ferritin, D-dimer and C-reactive protein (for each p < 0.001). Conclusion: No difference was observed among laboratory parameters, intensive care admission, intubation need, complication frequency and survival rates in patients with CSD or cancer.