Infectious enteritis is highly prevalent among dogs worldwide and, in some cases, it can be fatal. This study describes the clinical and laboratorial findings of single and mixed infections associated with severe enteritis in 76 dogs from Southern Brazil. Intestinal segments and/or fecal samples were subjected to histopathology and molecular detection of DNA viruses, bacteria and protozoa. Severe intestinal lesions were observed in most cases. Single infections were detected in 52.6% of cases, double (36.8%) and triple (10.5%) infections were also identified. Carnivore protoparvovirus 2 (CPV-2) was the most frequent agent in single infections (36.8%). Coinfection by CPV-2 and Giardia spp. was the most common in dual infections (19.7%), followed by CPV-2 and Cryptosporidium spp. (10.5%). The most frequent triple infection was CPV-2, Giardia sp. and Cryptosporidium spp. (6.6%). Our results shown that single and mixed infections are associated with severe enteritis in dogs in southern Brazil, mainly involving CPV-2 and Giardia sp.