In this work we investigated the influence of CuO loading and catalyst pretreatment procedure to derive an optimal CuO-CeO2 catalyst for water-gas shift (WGS) reaction, and to study in detail structure-activity relationships. Nanostructured catalyst samples prepared by co-precipitation and a 10, 15 and 20 mol% CuO content were examined by XRD, BET and TPR/TPD analyses and subjected to pulse WGS activity tests in the temperature range of 180-400 deg C. As evaluated by TPR/TPD and N2O chemisorption analyses, with increasing CuO loading the portion of finely dispersed CuO nanoparticles decreases on behalf of larger CuO aggregates. Strong surface structure-activity dependence in WGS reaction was observed for all catalyst samples. It was established that increasing CuO content results in higher extent of CeO2 reduction, which has a positive effect on H2 production during the WGS reaction. Increasing calcination temperature on the other hand reduces BET surface area, induced by CuO sintering and agglomeration of CeO2 particles resulting in a negative effect on H2 production. Distinctive WGS activity dependence on surface acidity of examined solids was observed for all CuO loadings.