Background. The aim of this paper is to analyze the role of the biomarkers Interleukin 6, Tumoral Necrosis Factor a, sCD40L, high sensitive Troponin T, high sensitive C-Reactive Protein and Galectin-3 in predicting super response (SR) to Cardiac Resynchronization Therapy (CRT), as they have not been studied in this field before. Methods. Clinical, electrocardiographic and echocardiographic data was obtained preimplant and after one year. SR was defined as reduction in LVESV = 30% at one year follow-up. Blood samples were extracted preimplant. Multivariate logistic regression and ROC curves were performed. Results. 50 patients were included, 23 (46%) were SR. Characteristics related to SR were: female (35 vs. 11%, p = 0.04), suffering from less ischemic cardiomyopathy (13 vs. 63%, p < 0.0001) and lateral (0 vs. 18%, p = 0.03), inferior (4 vs. 33%, p = 0.01) and posterior infarction (0 vs. 22%, p =0.01); absence of mitral regurgitation (47% vs. 22%, p = 0.04), wider QRS width (157.7 +/- 22.9 vs. 140.8 +/- 19.2 ms, p =0.01), higher concentrations of sCD40L (6.9 +/- 5.1 vs. 4.4 +/- 3.3 ng/mL, p= 0.02), and left ventricular lead more frequent in lateral medial position (69 vs. 26%, p = 0.002). QRS width, lateral medial position of the lead and absence of mitral regurgitation were independent predictors of SR. sCD40L showed a moderate direct correlation with SR (r = 0.39, p = 0.02) and with the reduction of LVESV (r = 0.44, p = 0.02). Conclusion. sCD40L correlates significantly with SR to CRT. QRS width, absence of mitral regurgitation and lateral medial position of the lead are independent predictors of SR in this cohort.