Simple SummaryCaffeine is a stimulant used in humans and animals to improve newborns’ respiratory and neurological responses. The use of caffeine after birth could increase neonate survival. However, due to the immature systems of animals at birth, caffeine use can have different results. This review aims to understand caffeine’s effects on respiratory and neurological systems in neonate animal models (rat and mouse pups, goat kids, lambs, and piglets).AbstractCaffeine is widely used to improve neonatal health in animals with low vitality. Due to its pharmacokinetics and pharmacodynamics, caffeine stimulates the cardiorespiratory system by antagonism of adenosine receptors and alteration in Ca+2ion channel activity. Moreover, the availability of intracellular Ca+2also has positive inotropic effects by increasing heart contractibility and by having a possible positive effect on neonate vitality. Nonetheless, since neonatal enzymatic and tissular systems are immature at birth, there is a controversy about whether caffeine is an effective therapy for newborns. This review aims to analyze the basic concepts of caffeine in neonatal animal models (rat and mouse pups, goat kids, lambs, and piglets), and it will discuss the neuroprotective effect and its physiological actions in reducing apnea in newborns.