Today, New Psychoactive Substances (NPS) are increasingly being related to post-mortem cases, and this problem drastically intensifies as a result of the New Synthetic Opioids (NSOs) surge. Among NSOs, fentanyl derivatives (FDs) consist in a myriad of drugs with a high turnover. FDs detection in human biological samples is complicated by low concentrations and usual extensive metabolism. In this challenging context, this manuscript aims to report analytical data about two poorly documented FDs: benzoylfentanyl (BZF) and parafluorobutyrfentanyl (pFBF). In 2018, these FDs were identified in three samples (powders and blotting papers) in France. Nuclear magnetic resonance and liquid chromatography with high-resolution mass spectrometry detection (LC-HRMS) data including observed mass spectrometric fragmentation patterns were obtained. In addition, metabolites were investigated using human liver microsomes incubations and LC-HRMS analysis: norBZF, despropionylfentanyl and a hydroxylated-BZF were identified (and observed in hair) as BZF metabolites; norpFBF, parafluorofentanyl and a hydroxylated-pFBF were identified as pFBF metabolites. In the worrisome context of NSOs detection, these preliminary data can be useful for toxicologists.