Coronavirus disease 2019 (COVID-19) triggers important changes in routine blood tests. In this retrospective case-control study, biochemical, hematological and inflammatory biomarkers between March 10, 2020, and November 30, 2020 from 3969 COVID-19 patients (3746 in the non-intensive care unit (non-ICU) group and 223 in the ICU group) were analyzed by dividing into three groups as spring, summer and autumn. In the non-ICU group, lymphocyte to monocyte ratio was lower in autumn than the other two seasons and neutrophil to lymphocyte ratio was higher in autumn than the other two seasons. Also, monocyte and platelet were higher in spring than autumn; and eosinophil, hematocrit, hemoglobin, lymphocyte, and red blood cells decreased from spring to autumn. In the non-ICU group, alanine aminotransferase and gamma-glutamyltransferase gradually increased from spring to autumn, while albumin, alkaline phosphatase, calcium, total bilirubin and total protein gradually decreased. Additionally, C-reactive protein was higher in autumn than the other seasons, erythrocyte sedimentation rate was higher in autumn than summer. The changes in routine blood biomarkers in COVID-19 varied from the emergence of the disease until now. Also, the timely changes of blood biomarkers were mostly more negative, indicating that the disease progresses severely. The study was approved by the Erzincan Binali Yildirim University Non-interventional Clinical Trials Ethic Committee (approval No. 86041) on June 21, 2021.