Despite prophylactic anticoagulant treatments, thrombotic complications may develop in patients with coronavirus disease 2019 (COVID-19). This study aimed to evaluate the factors influencing anti-factor Xa activity in COVID-19 patients receiving low molecular weight heparin (LMWH). We prospectively evaluated 80 COVID-19 patients, diagnosed using polymerase chain reaction test, who were admitted to our clinic and administered LMWH; LMWH (enoxaparin) was applied according to the weight, D-dimer levels, and clinical condition of patients. Anti-factor Xa activity in blood, drawn 4 h after the 3rd dose of LMWH, was measured and an activity of < 0.2 IU/mL was considered subprophylactic. Patients were followed up clinically, and anti-factor Xa activity was re-examined before discharge. Groups 1 and 2 included 13 and 67 patients with subprophylactic (mean ± SD: 0.18 ± 0.06) and prophylactic (mean ± SD: 0.43 ± 0.23) anti-factor Xa activity, respectively. The proportion of eosinophils in patients was significantly higher in group 1 than in group 2 (mean ± SD; 2.96 ± 2.55 vs 0.90 ± 1.28; p = 0.001). At the time of discharge, the eosinophilic proportion of patients was significantly higher (eosinophil %, mean ± SD; 3.06 ± 1.49 vs 2.07 ± 1.92; p = 0.001), but the activated partial thromboplastin time was significantly lower (22.34 ± 1.38 vs 24.38 ± 3.58; p = 0.01) in group 1 than in group 2. Of 14 patients with eosinophil content > 4%, 6 were in group 1 ((6/13) 46.2%), while 8 were in group 2 ((8/63) 11.9%); ( p = 0.009), and all had a D-dimer level < 1 μg/mL ( p = 0.03). ROC analysis for the presence of anticoagulation at subprophylactic level revealed an area under curve of 0.79 (95% CI: 0.64–0.93); p = 0.001). In conclusion; Elevated eosinophil count is related to lower anti-factor Xa activity in patients with COVID-19 receiving LMWH. The clinical significance of the subprophylactic anti-factor Xa activity should be studied in COVID-19 patients (NCT04507282).