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Infectious diarrhea is one of the leading causes of fatal outcomes in young children. Differential diagnostics of such infections within the first hours of illness poses significant objective obstacles. Data from laboratory studies of autopsy material and pathological studies provide valuable information for understanding the spectrum of differential diagnostics and etiological structure of infectious diarrhea with fatal outcomes in young children. Materials and methods. There were analyzed 100 cases of fatal outcomes in children under the age of six years registered in Russia from November 2011 to December 2019, who was diagnosed with infectious diarrhea at different levels of the healthcare system. The data were assessed based on available medical case reports and the laboratory testing of autopsy samples performed by using nucleic acid amplification methods. Results. The diagnosis of infectious diarrhea was revised in 24 patients, based on the data of a set of intravital and post-mortem studies. In patients with unconfirmed diagnosis of acute intestinal infections, pneumonia was the most often detected — in 45.8% (11/24), sepsis — in 29.2% (7/24), meningitis/meningoencephalitis, acute surgical pathology and asphyxiation associated with vomit aspiration — in 16.7 % (4/24) cases. The causative agents of infectious diarrhea were identified in 71 of 76 patients with confirmed diagnosis of acute intestinal infections. Most prevalent were group A rotaviruses — 52.6% (40/76), group F adenoviruses — 17.1% (13/76), and noroviruses — 13.2% (10/76). Combination of pathogens was detected in 29 cases (38.2%). Prehospital lethal outcomes in patients with infectious diarrhea were observed in 17 cases (22.4%). In total, rate of neonatal deaths due to acute intestinal infections accounted for 62.2% and 2-year-old toddlers — 20.3%. 64 of 76 (84%) children had no unfavorable premorbid background. The most common pathologies associated with infectious diarrhea with developing fatal outcomes were pneumonia (including aspiration pneumonia) in 22.4% (17/76) and aspiration asphyxia in 6.6% (5/76). Hemolytic-uremic syndrome associated with diarrhea was diagnosed in 7.9% (6/76) of children. Conclusions. Within the first years of life children comprise a risk group for developing fatal outcomes during infectious diarrhea. Lack of unfavorable premorbid background should not be considered as a reliable positive prognostic criterion. Diagnostics of pneumonia should be included in the mandatory examination plan for children with severe infectious diar rhea. Based on study of clinical and autopsy material, group A rotaviruses were the lead causative agents among those resulting in infectious diarrhea with fatal outcomes in young children. Special attention should be paid to preventing vomit aspiration within the first days after disease onset.