The thermodynamics of small-molecule (H2, arene, alkane, and CO) addition to pincer-ligated iridium complexes of several different configurations (three-coordinate d8, four-coordinate d8, and five-coordinate d6) have been investigated by computational and experimental means. The substituent para to the iridium (Y) has been varied in complexes containing the (Y-PCP)Ir unit (Y-PCP = η3-1,3,5-C6H2CH2PR22Y; R = methyl for computations; R = tert-butyl for experiments); substituent effects have been studied for the addition of H2, C−H, and CO to the complexes (Y-PCP)Ir, (Y-PCP)Ir(CO), and (Y-PCP)Ir(H)2. Para substituents on arenes undergoing C−H bond addition to (PCP)Ir or to (PCP)Ir(CO) have also been varied computationally and experimentally. In general, increasing electron donation by the substituent Y in the 16-electron complexes, (Y-PCP)Ir(CO) or (Y-PCP)Ir(H)2, disfavors addition of H−H or C−H bonds, in contradiction to the idea of such additions being oxidative. Addition of CO to the same 16-electron complexes is also disfavored by increased electron donation from Y. By contrast, addition of H−H and C−H bonds or CO to the three-coordinate parent species (Y-PCP)Ir is favored by increased electron donation. In general, the effects of varying Y are markedly similar for H2, C−H, and CO addition. The trends can be fully rationalized in terms of simple molecular orbital interactions but not in terms of concepts related to oxidation, such as charge-transfer or electronegativity differences.