Neonatal puppies and kittens have physiological and anatomical characteristics that differ from those of adult animals, which impacts the interpretation of physical examination and complementary tests. The veterinarian must be familiar with the clinical, laboratory, and imaging aspects observed in neonates. It is necessary to thoroughly evaluate the litter and the mother to notice the most subtle signs of illness and advise the owner to constantly monitor the newborns, quickly sending them to specialized care. This review describes how to perform clinical assessments of newborns systematically and recognize clinical signs of neonatal changes or affections in puppies and kittens.