Diarrheal disease continues to be a leading cause of death in children under five years old in developing countries, where it is responsible for the death of approximately half a million children each year. Establishing the cause of diarrheal disease can be difficult in developing areas due to the lack of diagnostic tests, and thus empirical therapies are often required. In these settings, the choice of antibiotic (or the choice to not give it) depends on suspected agents, host conditions and local epidemiology. Herein, we report a representative case of a ten-month-old male patient with severe acute malnutrition (SAM) admitted to the Emergency Paediatric Clinic in Port Sudan for amoebic dysentery complicated by hypovolemic shock and sepsis, treated by target therapy for Entamoeba histolytica infection associated with empiric antibiotic therapy. Due to the absence of clinical improvement, Ciprofloxacin was added to the first-line treatment. This case highlights that in low-income countries amoebiasis, especially in children with SAM, may result in life-threatening complications. Although stool microscopy remains the most used diagnostic test in these settings, a novel inexpensive, easy to use and rapid diagnostic test would be warranted to reach a microbiological diagnosis and guide clinical decision. Further studies will be necessary to identify the patterns of antimicrobial resistance in order to appropriately manage these complicated cases.