Lower respiratory tract infections (LRTIs) are a significant cause of morbidity and mortality in pediatric populations worldwide. This study examines cerebral oxygenation (StO) in children with LRTIs using Time-Domain Near-Infrared Spectroscopy (TD-NIRS) device (PIONIRS S.r.l., Milan, Italy), a non-invasive tool that allows for measurement of cerebral StOin real-time. An observational case-control study was conducted, including 60 participants: 30 patients with LRTIs and 30 age and sex matched controls. We evaluated the correlation between cerebral StO and various clinical and physiological parameters and we used a multivariate logistic regression analysis explore predictors of LRTI. Cerebral StO was one of the key and independent predictors of LRTIs (OR = 0.45, p = 0.002) suggesting it could be an additional parameter to record for better assessing the condition of LRTI patients. These findings highlight the role of TD-NIRS in providing deeper insights into brain oxygenation in pediatric patients, independent of peripheral measurements such as peripheral oxygen saturation (SpO).