Abstract: Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which lead to impaired chloride (Cl-) movement across the plasma membrane. Individuals with CF typically excrete sweat with substantially higher Cl- and sodium (Na+) concentrations than healthy individuals. CF can lead to multi-organ manifestations, either primarily or secondarily (i.e. bronchiectasis, diabetes mellitus, osteoporosis, malnutrition, depression). Exercise is recommended as adjunctive treatment for many of these manifestations and exercise capacity has been shown to be an independent factor in CF survival. With the recent approval of highly effective CFTR modulators (HEMT) for 90% of CF patients, it is likely that survival for CF patients will increase substantially and it is anticipated that many patients will survive into their sixties. The efficacy of HEMT has led to some unintended consequences such as that some patients have become obese (BMI>30) and many have become less adherent to their daily airway clearance regimen and rely on exercise for airway clearance. These factors underscore the importance that regular vigorous exercise will play in ongoing care of CF patients, which is now expected to last many more decades. Since excessive water and electrolyte losses can contribute to dehydration and electrolyte imbalance, CF patients are at high risk for severe dehydration and electrolyte loss which can have deleterious consequences and limit intensity of exercise. There is substantial data that has described sweat rates and electrolyte loss in response to exercise in normal athletes, however, there is limited data for CF patients. We recently reported a novel skin-interfaced wearable microfluidic device and smartphone image processing platform that enables analysis of regional sweating rate and sweat chloride loss in athletes and CF pediatric patients in a mode that is comfortable and imperceptible to the wearer. We hypothesize that continuous electrolyte and sweat rate measurements captured with our soft wearable microfluidic sensors and smartphone application (called the CF Patch System) will provide actionable hydration and electrolyte repletion information for adult CF patients during exercise. The CF Patch wearable platform offers a groundbreaking approach for the quantitative and continuous assessment of CF hydration and health conditions. The foundational insights from this work will enable new care management paradigms for CF patients in remote settings.