Background: Potatoes react very sensitive to drought during growth, and appropriate plant stress responses may affect metabolites associated with the health quality of tubers.Objective: The aim of this study is to determine the effects of drought stress (DS) on soluble sugars, starch, crude protein, minerals, free amino acids (AAs) and fatty acids (FAs).Design: The experiment was carried out on three potato genotypes during two years with four replications. The plants were grown in pots, in a glasshouse with optimal water supply and under drought stress conditions. After harvest, the tubers of these two variants were analyzed for bioactive compounds relevant to non-communicable diseases (NCDs). Results: Apart from genotypic differences in most parameters, the results revealed that the DS caused a decline in glucose and fructose (P < 0.05, all) in both years, whereas sucrose was increased, especially in the second year with severe stress (P < 0.01). Starch was significantly reduced by moderate stress in the first year (P < 0.01), but less affected in the second year. Crude proteins and total amounts of free amino acids (AAs) were clearly enhanced by the stress in both years (P < 0.05, all), similarly as the minerals magnesium (Mg), potassium (K) and phosphorus (P) (P < 0.05, all), whereas calcium (Ca) declined (P < 0.05). The portion of α-linolenic acid (ALA) on total lipids was elevated in the stress variants (P < 0.01), while oleic acid (OLA), its precursor decreased significantly (P < 0.05), but only in the first year. In the second year, ALA was in general higher and not further induced by the stress. Also OLA was less affected in that year, similarly as all other FAs in both years. Interestingly, Myo-inositol (MI) and lipid acyl hydrolases (LAH) associated with modulation in cell membrane lipids raised by the drought stress in each year (P < 0.01, all). In the second year, MI and LAH data of the drought stressed tubers correlated significantly (r = 0.90, P < 0.01) indicating their joined action within plant stress responses.Conclusions: The biochemical changes induced by DS are not alarming with regard to NCDs. Decline in glucose, fructose and starch, and increase in crude proteins, free AAs, ALA, MI and minerals like Mg, K and P, on the other side, is profitable for the health benefits of tubers. However, a better quality is associated with a decrease in tuber yield.Keywords: potato, drought stress, bioactive compounds, chronic diseases