The interactions of copper(II) with N-alkyl-pyridine-2-carboxamides (M) were studied by electrospray ionization mass spectrometry. The influence of solvent and counter ion (Cl−, ClO4−) on the type of ions (complexes) observed was discussed. By cone voltage increase, the fragmentation “in source” of the ions discussed was achieved. In methanol solution containing N-alkyl-pyridine-2-carboxamide (M) and CuCl2 the singly- and doubly charged-ions [M + CuCl]+ and [M2 + Cu]+2 were detected. In acetonitrile solution containing N-alkyl-pyridine-2-carboxamide and CuCl2, the copper(I)-containing ions [M + CH3CN+Cu]+ were formed. The use of Cu(ClO4)2 instead of CuCl2 resulted in more abundant doubly-charged ions in both methanol and acetonitrlile solutions and, for the former solution, the ions containing methoxyl anion, namely [M + CuOCH3]+, were observed. When water was used as a solvent, the abundant ions corresponding to the protonated ligands were formed, while the ions corresponding to copper complexes were characterised by low abundances.