To protect human health, limits for the concentrations of per- and polyfluoroalkyl substances (PFAS) in drinking water are decreasing in many countries. However, the required treatment to achieve these lower concentrations is more resource and energy intensive than conventional drinking water treatment. Consequently, this intensified water treatment has an indirect negative impact on human health. For example, treatment with granular activated carbon (GAC), commonly used for PFAS removal, can lead to particulate matter emissions and additional global warming. These negative impacts partly off-set the health benefit achieved by lower PFAS exposure via drinking water. In this study, we quantified health impacts of both the increased treatment and the reduced PFAS exposure in disability-adjusted life years (DALYs), to assess whether PFAS removal from drinking water to specified targets with GAC results in a net health benefit. We selected the prospective Dutch drinking water guideline for PFAS of 4.4 ng PFOA-equivalent (PEQ) L−1, as this guideline is amongst the more conservative concentration targets globally. We first conducted a Life Cycle Assessment (LCA) to quantify the health cost associated with the increased reactivation frequency of an existing GAC system in the Netherlands, required to achieve PFAS concentrations below 4.4 ng PEQ L−1. Then, we quantified the health benefit obtained by the corresponding lower PFAS exposure, using pharmacokinetic modelling combined with published dose–response relationships. For the treatment plant investigated in the current study, which uses reactivated wood-based GAC, increasing the reactivation frequency to remove more PFAS was found to result in a net health benefit of 6.9–300 DALYs per 106 persons per year. However, when single-use rather than reactivated GAC would be used for PFAS treatment, the health losses from the GAC production were in the same range as the health benefits from lower PFAS exposure. Overall, the negative health impacts associated with more intensive water treatment should be considered when developing strategies to reduce PFAS exposure.