The etiopathogenesis of endometritis in mares and cows differs significantly; this could depend on a different sensitivity and reactivity of the uterus but also on endocrine and rearing factors and different stress sources. In both species, microorganisms and the immune system play a primary role in the generation of this pathology. Microbiological and cytological tests support clinical examination and significantly improve diagnostic accuracy. For both species, during the inflammation, immune cells invade the endometrium and release bioactive substances to contrast primary or secondary pathogen contamination. These molecules are traceable to cytokines, chemokines, and prostaglandins as well as reactive oxygen and nitrogen species (ROS and RNS), collectively known as RONS. The RONS-mediated oxidation causes morphological and functional alterations of macromolecules, such as proteins, lipids, and nucleic acids, with the consequent production of derivative compounds capable of playing harmful effects. These bioactive molecules and by-products, which have recently become increasingly popular as diagnostic biomarkers, enter the bloodstream, influencing the functionality of organs and tissues. This review has collected and compared information obtained in cows and mares related to the diagnostic potential of these biomarkers that are assessed by using different methods in samples from either blood plasma or uterine fluid.