Cardiac arrest (CA) survivors often develop long-term neurological deficits, but its long-term impact on vulnerable brain regions and neurological outcomes remains unclear. In a previous CA model with conventional cardiopulmonary resuscitation, we found reduced heme oxygenase (HO) activity in the hippocampus and cortex 14 days post-CA, suggesting its potential as a functional outcome marker. Here, we used a rat model with 6 or 8 min of CA followed by extracorporeal cardiopulmonary resuscitation. While in the 6 min-CA group, 67% survived to day 14, increased mortality within 4 days resulted in only 33% survival in the 8 min group post-ROSC. All animals displayed neurological impairment assessed by daily neurologic deficit scoring (NDS). While deficits declined within the first 3–4 days in the 6 min-CA animals, the 8 min-CA group showed significantly worse neurological outcomes until day 14. Two weeks post-CA, neuroinflammatory and neurodegenerative markers (HO-1, TNF-R1, Iba1, and GFAP) were elevated in the hippocampus, while HO and 2-oxoglutarate dehydrogenase complex activities were reduced in all rats, indicating a decrease in anti-oxidative capacity and mitochondrial capacity for metabolizing glutamate. NDS at day 4–5 strongly correlated with the delayed CA-mediated enzymatic dysfunction determined in the hippocampus. This finding highlights this time point for identifying at-risk individuals and suggests a prolonged therapeutic intervention lasting at least until 4 days post-CA.