Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) indicate that over 65% of adults aged 51–70 years in the U.S. do not meet hydration criteria. They have hyponatremia (serum sodium < 135 mmol/L) and/or underhydration (serum sodium >145 mmol/L, spot urine volume <50 mL, and/or spot urine osmolality ≥500 mmol/kg). To explore potential public health implications of not meeting hydration criteria, data from the NHANES 2009–2012 and National Center for Health Statistics Linked Mortality Files for fasting adults aged 51–70 years (sample n = 1200) were used to determine if hyponatremia and/or underhydration were cross-sectionally associated with chronic health conditions and/or longitudinally associated with chronic disease mortality. Underhydration accounted for 97% of the population group not meeting hydration criteria. In weighted multivariable adjusted Poisson models, underhydration was significantly associated with increased prevalence of obesity, high waist circumference, insulin resistance, diabetes, low HDL, hypertension, and metabolic syndrome. Over 3–6 years of follow-up, 33 chronic disease deaths occurred in the sample, representing an estimated 1,084,144 deaths in the U.S. Alongside chronic health conditions, underhydration was a risk factor for an estimated 863,305 deaths. Independent of the chronic health conditions evaluated, underhydration was a risk factor for 128,107 deaths. In weighted multivariable Cox models, underhydration was associated with 4.21 times greater chronic disease mortality (95% CI: 1.29–13.78, p = 0.019). Zero chronic disease deaths were observed for people who met the hydration criteria and did not already have a chronic condition in 2009–2012. Further work should consider effects of underhydration on population health.