Background: Elevated concentrations of plasma copeptin, a marker for vasopressin and a known risk factor for diabetes development, is observed in individuals with low water intake. In this study, we hypothesized that water supplementation (1.5 L day-1) over a period of six weeks could lower fasting plasma copeptin (PCop) and possibly impact glucose (PGluc) concentrations in habitual low-drinkers. Design and method: Stored plasma samples collected between 2013 and 2015 in the ongoing population study Malmö Offspring Study (MOS) were screened for high copeptin concentrations (PCop ≥ 10.7 pmol L-1 in men and ≥ 6.1 pmol L-1 in women). Twenty-four percent of the MOS population presented high concentrations of copeptin; among these, thirty-one healthy adults with low fluid intake habits at the baseline of the current study (24h urine volume ≤ 1.5L and 24h urine osmolality ≥ 600 mOsm kg-1) were enrolled 2.8 ± 0.8 years after MOS screening. At baseline and at the end of the six-week intervention, fasting plasma samples, food and fluid diaries, and 24h urine samples were collected. Pre- vs post-intervention differences were assessed with paired t-test or Wilcoxon’s paired rank test where appropriate. Unless stated otherwise, data are presented as median [25th; 75th percentiles]. Results: The water intervention succeeded in increasing mean (95% confidence interval) plain water intake from 0.43 (0.27; 0.58) to 1.35 (1.00; 1.71) L day-1 (P < 0.001), on top of habitual fluid intake, with no other changes in diet. Urine osmolality, as a marker of urine concentration, was reduced from 879 [705; 996] to 384 [319; 502] mOsm kg-1 (P < 0.001), and urine volume increased from 1.06 [0.90; 1.20] to 2.27 [1.52; 2.67] L d-1; P < 0.001. At baseline, PCop was 12.9 [7.4; 21.9] pmol L-1 and did not differ from the values obtained during the population screening of MOS three years earlier. At the end of intervention, PCop was significantly reduced to 7.8 [4.6; 11.3] pmol L-1; P < 0.001. The reduction of PCop was most pronounced in subjects belonging to the top tertile of baseline PCop (△PCop 28.2 (8.1 – 58.6)), as compared to subjects in PCop tertiles 1+2 (△PCop1.6 (-0.3 – 4.5)), P < 0.001. Finally, water supplementation significantly reduced mean (SD) plasma glucose (PGluc) from 5.94 (0.44) to 5.74 (0.51) mmol L-1; P < 0.05. The reduction of PGluc was most pronounced in subjects belonging to the top tertile of baseline PCop (Figure 1). Conclusion: Water supplementation in habitual low-drinkers with high copeptin appears as an effective and safe way to lower copeptin concentration. Given the suggested role of vasopressin in diabetes development, increasing water may be a promising intervention with potential of lowering fasting plasma glucose. Further investigations are warranted to support the present findings.