Background: Among the serum biomarkers of infectious diseases, calprotectin and heparin-binding protein (HBP) seem to be of clinical and diagnostic value in patients with COVID-19. Objectives: This study aimed to investigate the serum levels of calprotectin, HBP, and some other inflammatory markers in COVID-19 patients. Methods: In this case-control study, serum samples of 35 outpatients with COVID-19 and 35 healthy individuals were collected, and the levels of calprotectin, HBP, C-reactive protein (CRP), ferritin (FERR), as well as platelet (PLT) and neutrophil (NEU) counts and LDH activity, were determined. Results: At first, SARS-CoV2 viral RNA was detected in the pharyngeal swab specimens of COVID-19 patients. Calprotectin, FERR, and CRP levels, LDH activity, and PLT and NEU counts were found to be significantly higher in COVID-19 patients compared with controls (P < 0.05), whereas no statistically significant difference was observed in HBP level (P > 0.05). Serum calprotectin showed a significant correlation with CRP and FERR levels, LDH activity, and NEU count (P < 0.001). Conclusions: Our findings showed that an increment in serum calprotectin level, together with increased CRP levels, might be a promising indicator of SARS-CoV2 infection.