BACKGROUND: Although the circadian rhythm is known to influence several neurological diseases and response to treatments, its potential impact on brain injury following cardiac arrest and cardiopulmonary resuscitation (CA/CPR) remains unclear. METHODS: We performed a retrospective observational study on out-of-hospital cardiac arrest (OHCA) cases that presented to the emergency department of our hospital between September 2022 and August 2024. Based on the CA/CPR onset time, all patients were divided into two cohorts: daytime and nighttime groups. The gray-to white-matter signal intensity ratio (GWR) was analyzed using brain computed tomography (CT) images. We used the Cerebral Performance Category (CPC) to estimate the neurological outcomes. C-reactive protein (CRP), white blood cell (WBC) count, and monocyte (MONO) count levels in the plasma were also analyzed. RESULTS: Our study included 138 patients, of whom 68 were subjected to CA/CPR during daytime (8:00 to 20:00) and the remaining 70 were subjected to CA/CPR during nighttime (20:00 to 8:00). The imaging data showed that GWR values were significantly lower among patients subjected to CA/CPR during nighttime compared to those who were subjected to CA/CPR during daytime. Consistently, lower survival rates were observed among nighttime CA/CPR survivors. The CPC results indicated that a greater number of patients who underwent CA/CPR during daytime were rated as class 1-2 on day 3, day 5, and day 7 after achieving return of spontaneous circulation (ROSC). In contrast, a larger proportion of CA/CPR survivors in the nighttime group were rated as class 5 at the same time points. Elevated levels of C-reactive protein, white blood cell count, and monocyte count were observed in the plasma of survivors who underwent nighttime CA/CPR. CONCLUSION: We found that patients subjected to CA/CPR during nighttime (20:00-8:00) had worse neurological outcomes compared to those treated during daytime (8:00-20:00).