In this study, alkali metal-doped sepiolite based catalysts were developed for the up-grading of ethanol through the Guerbet reaction mechanism. The catalysts were prepared by wetness impregnation with aqueous solution containing alkali metal precursors salts over calcined sepiolite, and finally activated at 500ºC in air. The catalysts have been characterized by XRD, SEM-EDS, TGA-DSC, N2-adsorption. In addition, TPD-CO2 and TPD-NH3 were used to determine the acid and basic characteristics of catalysts. The catalysts were tested into a quartz continuous gas-flow reaction system working at atmospheric pressure to investigate the effects of metal loading (wt%), the nature of the alkali metals and of the main reaction parameters (e.g., reaction temperature, weight hourly space velocity), on the production of n-butanol starting from ethanol. The highest yield (18%) was obtained at 400 ºC with the catalyst consisting in sepiolite, calcined at 500ºC, impregnated with 7 wt% of Cs. This study proves that ad hoc modified natural sepiolites with alkali metals are effective catalysts for the Guerbet upgrading of ethanol. Display omitted •Alkali-metal modified sepiolite was used as catalyst for the Guerbet conversion of ethanol.•Alkaline metals modified sepiolite acid-base properties changing products distribution.•The catalysts containing ca0.06 mmolMe/gsep of alkali metals were the more selective to n-butanol.•The Cs-doped sepiolite containing 7 wt% of metal led to the highest yield of n-butanol.