Pharmaceutical monitoring (37 pharmaceuticals and 3 human tracers) was conducted in a headwater streams in southwest France, an area characterized by a low population density with an elderly population (30% > 60 years old) and extensive agriculture (cow cattle breeding). Polar Organic Chemical Integrative Sampler (POCIS) were exposed for 14-day consecutive periods in 2016 at three sampling points. Three human wastewater tracers and 20 pharmaceuticals commonly used for human and/or cattle were quantified in headwaters. Succession of small Wastewater Treatment Plant (WWTP), non-collective sanitation, discharges of untreated effluents as well as the river ability to dilute discharged wastewater, mainly explain the pharmaceuticals and human tracers concentrations. Pharmaceutical loads were time-dependent and were higher during cold season due to increase of pharmaceutical consumption. In contrast, better degradation and/or sorption onto river biofflms in warm season induced the decrease of headwater pharmaceutical content. The headwaters streams were contaminated by compounds found in other type of watershed, but beta-blocker were the compounds quantified in higher concentration with frequencies of 100%, which was consistent with the elderly population living in the watershed. Specific compounds (sulfamerazine and sulfamethoxazole) used to cattle medical care were detected in waters, but at a low content.