Objectives: Data on baseline drug resistance important in informing future antimicrobial stewardship programs. So far, no data on the antimicrobial drug resistance of clinical isolates available for the African archipelago of Cabo Verde. Methods: We performed a retrospective analysis over years (2013-17) of the drug susceptibility profiles of clinical isolates in the two main hospitals of Cabo Verde. For Escherichia coli and Staphylococcus aureus, representing 47% and 26% of all clinical isolates, the antimicrobial drug resistance profile was reported for six representative drugs. Results: For E. coli we detected an increase in resistance to ampicillin, amoxicillin/clavulanic acid, ceftriaxone, ciprofloxacin and trimethoprim-and for S. aureus to methicillin, erythromycin and trimethoprim-sulfamethoxazole. This increase in both the most commonly isolated bacterial pathogens is alarm as it might compromise empirical treatment in a setting with limited access to laboratory testing. Conclusions: When compared to the published low resistance rates in carriage isolates, the more alarming situation in clinical isolates for S. aureus might encourage antimicrobial stewardship programs to reduce in hospital settings, possibly as part of the Cabo Verdean national plan against antimicrobial drug resistance.