The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been recognized as predictors of various critical illnesses. Our study aimed to investigate whether the NLR and PLR measured at different timepoints could predict poor neurological outcomes at 6 months. This observational retrospective cohort study included adults who had experienced out-of-hospital cardiac arrest (OHCA) and received targeted temperature management between November 2015 and December 2020. Patients with an active infection, as confirmed by an initial blood culture, were excluded. Multivariate logistic regression models were used to determine the association between the NLR and PLR at 0, 24, and 48 h after return of spontaneous circulation and poor neurological outcomes, defined as a Cerebral Performance Category score of ≥3 at 6 months. The NLR at 24 h, but not the NLR or PLR at other timepoints, was significantly associated with poor neurological outcomes (odds ratio: 1.05; 95% CI: 1.01–1.09; p = 0.018). The NLR at 24 h showed moderate accuracy in predicting poor neurological outcomes, with an AUC of 0.619. A cutoff value of 9.0 achieved 72.5% sensitivity and 47.7% specificity. The NLR measured at 24 h after ROCS could be used for early neuroprognostication given its low cost and widespread availability.