Icodextrin is a starch-derived glucose polymer used in peritoneal dialysis dialysate to treat volume overload by increasing ultrafiltration in patients with end-stage renal disease. Reported adverse reactions to icodextrin are mild and rare and mainly consist of skin rash that resolves spontaneously after discontinuation of treatment. We describe a young patient with extreme eosinophilia that appeared with the use of icodextrin, disappeared after its discontinuation, and reappeared after a rechallenge with the drug. The eosinophilia was not associated with peritonitis, was asymptomatic, and fully resolved after discontinuation of the drug. Severe eosinophilia can potentially cause tissue damage in several organs, which would indicate that blood eosinophil count is recommended in routine complete blood counts while icodextrin peritoneal dialysis is being administered.