Cardiac arrest (CA) entails significant risks of coma resulting in poor neurological and behavioral outcomes after resuscitation. Morbidity and mortality in post-CA patients are due largely to the cerebral dysfunction that accompanies prolonged whole-body ischemia called as post-CA syndrome (PCAS). PCAS involves strong inflammatory responses including neuroinflammation. Currently, there are no proven neuroprotective therapies to improve post-CA outcomes apart from therapeutic hypothermia. Furthermore, there are no acceptable approaches which can target neuroinflammation and lead to good neurological outcome post-CA. Moreover, delivering drugs across the blood-brain barrier to the target injured cells for treating diffuse brain injury is a major challenge. We hypothesize that dendrimer-based N-acetyl-L-cysteine (D-NAC) therapy ameliorates Neuroinflammation by specifically targeting activated glial cells and leads to a marked improvement in post-CA neurological outcome. we used an asphyxial CA rat model to determine the effects of D-NAC treatment. D-NAC was administered 30-minute post return of spontaneous circulation after cardiopulmonary resuscitation (ROSC). The behavioral neurologic deficit score (NDS score) was evaluated at 4, 24 and 48 hrs post-CA. CA resulted in a 50% decrease in survival and a dramatic decrease in NDS score acutely. D-NAC improved survival to 75% and led to a more rapid improvement in NDS scores when compared to the saline group in the short term while free NAC was not effective. We also tested long term (7 days) behavioral outcomes (novel object and fear conditioning) post-CA. Administration of D-NAC significantly improved novel object recognition and decreases freezing behavior in a novel context suggesting an improvement in cognitive deficits following CA in this model. In summary, acute administration of D-NAC following CA results in physiological and behavioral improvements both acutely and long term.