Background: SARS-CoV-2 triggers severe immune responses causing organ damage. It was detected in December 2019 and emerged as a global respiratory threat. Complete blood count (CBC) is crucial for assessing health, including RBC count, MCV, MCHC, MCH, and RDW. Objectives: The study aimed to analyze RBC-related parameters and their response to COVID-19 infection. Patients and methods: A case-control study including 200 with moderate COVID-19 cases and 100 controls who were healthy individuals if the same sex and age group. Blood samples were collected for various tests, including CBC, ferritin, CRP, LDH, PT, and D-Dimer. RT-PCR was used for SARS-CoV-2 detection from nasopharyngeal swabs. Results: In contrast to the control group, COVID-19 patients had significantly lower RBCs (P=0.002), hemoglobin (P=0.001), hematocrit value (P=0.005), MCHC (P=0.005), lymphocyte percentage (P=0.005), and lymphocyte count (P=0.001). However, they had significantly higher RDW, Neutrophil percentage, D-dimer, CRP, ferritin, and LDH than the control group. Patients showed marginally significant positive correlations between MCH and D-Dimer (P=0.011), RDW and LDH (P=0.007), and marginally significant negative correlations between RBCs and LDH (P=0.011). Conclusion:  Patients with COVID-19 showed higher levels of RDW, CRP, ferritin, and LDH, but lower levels of RBC count, hemoglobin, hematocrit, MCHC, and lymphocyte count, indicating that these markers offer valuable insights into the prognosis of COVID-19 patients. There were positive correlations between MCH and D-Dimer and between RDW and LDH. While there were negative correlations between Hb, RBCs, and LDH.