Despite recent identification of several prognostic markers, there is still a need for new prognostic parameters able to predict clinical outcome in chronic lymphocytic leukemia (CLL) patients. Here, we aimed to validate the prognostic ability of known (proteomic) markers measured pre-treatment, and to search for new proteomic markers that might be related to treatment response in CLL. To this end baseline serum samples of 51 CLL patients treated with chemo-immunotherapy were analyzed for 360 proteomic markers, using Olink technology. Median event-free survival (EFS) was 23 months (range 1.25-60.9). Patients with high levels of sCD23 (>11.27; p=0.026), sCD27 (>11,03; p=0.04), SPINT1 (>1.6; p=0.001), and LY9 (>8.22; p=0.0003) had a shorter EFS than those with marker levels below the median. The effect of sCD23 on EFS was different between immunoglobulin heavy chain variable gene mutated and unmutated patients, showing the shortest EFS for unmutated CLL patients with sCD23 levels above the median. Taken together, our results validate the prognostic impact of sCD23 and highlight SPINT1 and LY9 as possible promising markers for treatment response in CLL patients.Copyright © 2020. Published by Elsevier Inc.