The mechanism of dithiophosphinate (DTPI) adsorption on chalcopyrite was investigated by diffuse reflectance Fourier transformation (DRIFT) spectroscopy and by cyclic voltammetry (CV) at various pHs. CV experiments showed that the redox reactions occurred at a certain degree of irreversibility on the chalcopyrite surface in the absence of a collector due to preferential dissolution of iron ions in slightly acid solution and irreversible surface coverage by iron oxyhydroxides in neutral and alkaline solutions. In the presence of DTPI, CV experiments failed to identify the type of the adsorbed DTPI species and electrochemical processes occurring on chalcopyrite due to formation of an electrochemically passive surface layer preventing electron transfer. However, DRIFT spectroscopy tests showed this passive layer to be mainly CuDTPI + (DTPI)2. Both CV and DRIFT spectroscopy established that the activity of collector species decreased with increasing pH due to formation of stable hydrophilic metal oxyhydroxides on the chalcopyrite surface.