There is strong evidence that tobacco smoke inhibits both MAO A and MAO B isoforms in the body. However, which components of cigarette smoke are responsible for MAO inhibition is not clear yet. Our group has identified six previously unidentified candidate MAO inhibitors from the tobacco smoke. The MAO inhibitory effects of these candidate inhibitors were compared with that of nicotine and TPM (Tobacco Particulate Matter). An SH-SY5Y cell line was exposed to different regimens of ethanol (control), nicotine, TPM and the cocktail of candidate inhibitors. A final concentration 0.2 μM nicotine was used and the concentration of each candidate inhibitor was relative to that originally found in TPM. We found that nicotine did not have any significant MAO inhibitory effect compared to the control. TPM inhibited overall MAO activity by 39%, while the MAO inhibition by cocktail of candidate inhibitors was 47%. The results suggest that the candidate inhibitors identified by our group are the major contributors to the total MAO inhibitory activity depicted by cigarette smoke and potentially unlocks the mystery behind the components responsible for MAO inhibition by cigarette smoke in smokers.