Amoebiasis, a clinical condition caused by Entamoeba histolytica does not usually present with generalized oedema known as anarsarca. We present a case of an adolescent female Nigerian who was admitted on account of chronic diarrhea and anarsarca in a tertiary hospital, Southwest Nigeria. There was no proteinuria. She however had cyst of E. histolytica and growth of E. coli in her stool; she also had E. coli isolated in her urine. She had hypoproteinaemia (35.2g/L) and hypoalbuminaemia (21.3g/L) as well as hypokalemia (2.97mmol/L). Symptoms resolved and biochemical parameters normalized following treatment with Nitrofurantoin, Tinidazole and Ciprofloxacin. A mixed infection of Entamoeba histolytica and Escherichia coli bacteria may be responsible for the worse clinical manifestations of Amoebiasis