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Background: Fibulin 1 and Fibulin 2 are members of the extracellular matrix (ECM) glycoprotein family. ECMs drive prognosis through remodeling, a key step in the pathogenesis of heart failure (HF). We aimed to compare Fibulin 1 and 2 levels in different stages of HF and to investigate their relationship with other prognostic factors of HF. Methods: Patients with HF were divided into two groups according to left ventricular ejection fraction (LVEF): reduced and non-reduced LVEF. The control and patient groups consisted of individuals with Stages A and B HF, Stages C and D HF, respectively. Fibulin levels were measured at different stages of HF and in the control group. Additionally, Fibulin levels were measured at admission, discharge, and in the first month in patients who were hospitalized due to decompensated HF. Results: Serum Fibulin 1 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were significantly higher in the patient group than in the control group. Serum Fibulin 2 levels were similar between the groups. Although serum Fibulin 2 levels were similar at repeated measurements, serum Fibulin 1 and NT-proBNP levels significantly decreased at discharge and remained similar at 1 month compared with admission. There was a significant positive correlation between Fibulin 1 and NT-proBNP levels and a significant negative correlation between Fibulin 1 levels and LVEF. Fibulin 2 levels were not correlated with LVEF and NT-proBNP. Conclusions: Our study demonstrated that serum Fibulin 1 levels differ among different HF stages and have a similar temporal change as observed for NT-proBNP levels. A similar association was not observed for Fibulin 2 in our study.