Carboxylate-assisted Pd-catalyzed C-H bond activation constitutes a mild and versatile synthetic tool to efficiently and selectively cleave inert C-H bonds. Herein, we demonstrate a simple method to experimentally evaluate both reactivity and selectivity in such systems using mass spectrometry (MS) methods. The N-heterocyclic carbene (NHC) cations [(NHC)PdX]+, bearing as X- ligand bases commonly used to promote the C-H activation (carboxylates and bicarbonate), are generated in the gas-phase by ESI-MS. Their C-H bond activation at the N-bound groups of the NHC is then studied using Collision Induced Dissociation (CID) experiments. Ion Mobility Spectrometry (IM)-MS is exploited to identify a number of regioisomers associated with the distinctive site selective C-H activations. It is demonstrated that such C-H activation concomitant with acetic acid release occurs from a mixture of activated [(NHC-H)Pd(CH3CO2H)]+ and non-activated [(NHC)Pd(CH3CO2)]+ complexes. The identity of the X-type ligands (X = Cl-, carboxylates and bicarbonate) has a significant impact on the regioisomer branching ratio upon CID conditions. IM-MS in conjunction with a DFT mechanistic study is presented for the acetate-assisted C-H activation of the [(NHC)Pd(CH3CO2)]+ cation featuring butyl and aryl as N-donor groups. Ion Mobility Mass Spectrometry methods were employed to investigate the regioselectivity aspects of carboxylate-assisted Pd-mediated C-H activation of N-heterocyclic carbene ligands.