Introduction: Decreased plasma Lysophosphatidylcholine (LPC) was found to be associated with survival after cardiac arrest (CA) in humans and rats. Supplementing LPC species containing docosahexaenoic acid, LPC(22:6), improved rat brain function and survival after CA. Thus, LPC deficiency may be a major cause of CA pathology and LPC supplementation may be a novel therapeutic approach to CA. However, the therapeutic effects of individual LPC species are not fully understood, particularly a species containing linoleic acid, LPC(18:2). While 22:6 is an omega-3 fatty acid and highly abundant in the brain, 18:2 is omega-6 and minimally present in the brain. Therefore, we hypothesized that the protective role of LPC(18:2) may be different from LPC(22:6). Furthermore, LPC(18:2) may provide additive protection when administered together with LPC(22:6). Objective: To investigate the protective role of supplementing LPC(18:2) compared to LPC(22:6) after CA. Methods and Results: We first compared the relationship between plasma LPC(18:2) levels and outcomes of CA patients as compared to LPC(22:6). LPC(22:6) was found to be associated with both survival and neurological outcomes, whereas the levels of LPC(18:2) were associated with survival only. We then tested whether supplementing LPC(18:2) can improve survival and neurological function in rats undergoing 10 minutes of asphyxial CA. Supplementing LPC(18:2) post-resuscitation significantly improved survival as did LPC(22:6) in rats. Although LPC(18:2) supplementation improved in some individual neurofunctional tasks, the overall neurological function of survived rats was not improved. Particularly, while 3 of 7 survived rats treated with LPC(22:6) were able to walk across a ledge, none of 10 survived rats treated with LPC(18:2) were able to cross the ledge. Conclusion: Significantly improved survival without significantly improved brain function in rats and poor correlation with neurological outcomes from humans suggest that LPC(18:2) may protect organs other than the brain. The results further indicate that different LPC species have different mechanisms of improving outcomes, demonstrating the potential of utilizing different combinations of LPC as improved therapeutic treatments in CA.