Background/Objectives: Advanced calcific aortic stenosis, with or without coronary artery disease [CAD], may lead to severe systolic dysfunction. The aim of the study was to reveal clinical and laboratory parameters that may differentiate patients with severe aortic stenosis with and without systolic dysfunction. Methods: A retrospective, single-center study included all consecutive patients diagnosed with severe aortic stenosis with overt heart failure. Patients with hematological and neoplastic diseases were excluded. Demographic, clinical and laboratory data were analysed. Neutrophil-to-lymphocyte [NLR], monocyte-to-lymphocyte [MLR], and platelet-to-lymphocyte [PLR] ratios were calculated. The study group was divided based on left ventricular ejection fraction [LVEF]. Results: The final study population comprised 301 patients [133 males [44%]; median [Q1-3] age of 80 [75-83] years]. Co-morbidities included CAD [48.8%], arterial hypertension [75.4%], diabetes mellitus [n = 124, 41.2%], atrial fibrillation [39.2%], chronic kidney disease [60.8%]. Fifty-seven patients presented with LVEF ≤ 40% (heart failure with reduced ejection fraction (HFrEF)) and 244 with LVEF > 40%. In the multivariable analysis, N-terminal pro-B-type natriuretic peptide [NTproBNP] [p < 0.001, OR 1.000, 95%CI 1.000-1.000], baseline MLR [p < 0.020, OR 7.393, 95%CI 1.363-40.091] and female sex [p < 0.001, OR 0.308, 95%CI 0.160-0.593] were revealed as significant predictors of HFrEF. Baseline MLR weakly correlated with EuroScore II [Spearman r = 0.141, p = 0.015] and NTproBNP [r = 0.142, p = 0.014]. Cut-off values were established as 0.36 for MLR and 3927 pg/mL for NTproBNP. After excluding 147 patients with CAD, there was still a statistically significant difference in MLR between the subgroups [p = 0.024]. Conclusions: Increased values of MLR and NTproBNP together with female sex are predictive parameters for LVEF ≤ 40% in patients with severe aortic stenosis.