Complimentary UHPLC-MS methods for 6 ultra short chain (polar) and 30 long chain (and relatively non-polar) PFAS compounds have been developed and used to profile these compounds in human serum. The methods were developed to be rapid, with both having analysis times of ca. 5 min, to enable the rapid screening of samples. Both methods were sensitive enough to detect the target PFAS over the range 0.5–50 ng/mL. These methods were then applied to the screening of the serum of 137 subjects comprising healthy controls (HC), subjects with mild cognitive impairment (MCI) and those with Alzheimer's disease (AD). These methods demonstrated the presence of the 33 of targeted PFAS in these serum samples, presenting over a wide concentrations range with PFPrA found at the highest maximum concentration of 707 ng/mL. Interestingly the PFAS profiles found for the HC and MCI subjects differed from those of the AD patients. The reason(s) for differences in the PFAS profiles obtained for serum from AD patients compared to HC/MCI subjects is unclear and may be unrelated to disease but clearly warrants further investigation to clarify the underlying reasons for this observation.