The aim of the present study was to assess whether different functional virgin olive oils (FVOOs) with varying phenolic compounds (PC) could protect the plasmatic fat-soluble vitamins, which in turn could improve the endothelial function. In order to select the optimal phenolic dose in the improvement of ischemic reactive hyperemia (IRH), a dose-response study (n = 12, healthy subjects) was performed and the enrichment of 500 mg PC/kg oil was selected. In a 3-week cross-over sustained study (n = 33 hypercholesterolemic subjects), the consumption of 25 mL/day of two phenol-enriched olive oils (one enriched with its own PC and another combined with thyme PC) increased IRH and plasma concentrations of retinol, β-cryptoxanthin and α-tocopherol, compared to a control virgin olive oil. A positive post-intervention correlation was observed for IRH values and HDL-c, β-cryptoxanthin, lutein and α-tocopherol. Results suggest that preservation of plasmatic fat-soluble vitamins by PC from FVOOS could partially explain the endothelial function benefits. ; This study was supported by the Ministerio de Economia y Competitividad (AGL2012-40144-C03-02; AGL2012-4014-C03-01 and AGL2012-40144-C03-03 projects and AGL2009-13517-C03-01, AGL2009-13517-C03-02 and AGL2009-13517-C03-03 project), CIBEROBN, FPI fellowship (BES-2010-040766), ISCIII and Departament de Salut joint contract (CP06/00100). PI13/01848, integrado en el Plan Estatal de I+D+I 2013-2016 y cofinanciado por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). We thank Borges Mediterranean Group for providing the common olive oil used in the study. This work has been done in the context of Universitat Autònoma de Barcelona (UAB) PhD Program in Biochemistry, Molecular Biology and Biomedicine, Department of Biochemistry and Molecular Biology. Authors’ contributions to manuscript were as following: R-MV, MFi, RdlT, M-IC, M-JM, RS design research; R-MV, MFa, AP,SF-C, UC, LR, MR, MG, GT-S, MFi, RdlT, M-IC, M-JM, RS were responsible for the execution of the study including hands-on conduct of the experiments, data collection and interpretation of data; R-MV, AP, RS, LR drafted the manuscript and MFi, M-IC, M-JM, RS, LR revised the manuscript critically providing important intellectual content. RS has primary responsibility for final content. All the authors read and approved the final manuscript.