Background and Aims: Infective endocarditis (IE) is associated with several morbidities and high rate of mortality. Predicting these morbidities can be helpful in managing patients and can prevent possible complications, result from IE. In this study, we aimed to evaluate the association between C-reactive protein (CRP), N-terminal pro brain natriuretic peptide (BNP), monocyte to high density lipoprotein (HDL) ratio Charlson comorbidity index, and European System for Cardiac Operative Risk Evaluation (Euro SCORE) in complicated cases of IE. Materials and Methods: This prospective study was conducted on a referral center from January 2017 to December 2020. Patients with definite or possible diagnosis of IE based on the modified Duke criteria were included in this study. Demographic information and serum levels of N-terminal pro BNP, D-Dimer, CRP were evaluated in patients. In addition, we used Charlson comorbidity index and The Euro SCORE for subjective assessment. Results: One hundred and four patients (64 males, median age: 58) included in the final analysis. Intracardiac involvement, central nervous system (CNS) complications and systemic complications were observed in nine patients (9.7%), 16 patients (15.4%), and eight patients (7.7%) respectively. The mortality rate was 14.4%. D-dimer (P = 0.008), pro-BNP (P = 0.008), and Charlson criteria (P = 0.012) were higher in patients with systematic complications. In addition, NT pro-BNP was significantly associated with CNS complications (P = 0.04) and D-Dimer level was significantly associated with in-hospital mortality (P = 0.008). Conclusion: Serum biomarkers such as pro-BNP and D-dimer, and comorbidity indices can be used for risk stratification of patients with IE. The level of pro-BNP is significantly associated with CNS complications and the level of D-dimer is significantly with mortality in patients with IE.