© 2020 Elsevier Inc. Introduction: Covid-19 infection was declared a global pandemic by WHO on March 11, 2020. GRP78 protein is known to be involved in the intrusion of numerous viruses. Our current study tries to provide some insight into the variation of GRP78 protein levels in patients with Covid-19 (−) pneumonia, Covid-19 (+) pneumonia, and CT negative Covid-19 infection in comparison to the normal population through a larger number of cases. Materials and methods: 42 patients who have Covid-19 (−) pneumonia; 72 patients who have Covid-19 infection (30 pneumonia,42 CT negative patients) and 30 patient who have no known diseases (control group) have included in the study after the clinical and radiological evaluation. Serum GRP78 levels of the subjects were measured through a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results: The GRP78 level was found to be significantly higher in the Covid-19 infection group than both Covid-19 (−) pneumonia and control group (p = 0.031 and p = 0.0001, respectively).No significant difference was evident between Covid-19 (−) pneumonia, Covid-19 (+) pneumonia and CT negative Covid 19 infection groups with respect to GRP78 levels (p = 0.09). In addition, the GRP78 levels were significantly higher in the Covid-19 (−) pneumonia group than the control group (p = 0.0001). Conclusion: This prospective case-control study reveals that the serum GRP78 levels significantly increased during Covid-19 infection in comparison to both the Covid-19 (−) pneumonia and the control group. As the association between SARS-CoV-2 virus and GRP78 protein is revealed more clearly, this association may come to the fore as a therapeutic target.