Electrolytic changes in blood have been associated with the use of anti-epidermal growth factor receptor (EGFR) antibodies. The objective of this retrospective study was to compare the rate of incidence and the severity of blood electrolyte and protein imbalances occurring in patients receiving cetuximab or panitumumab with or without concurrent chemotherapy. Treatment data of 58 patients who received cetuximab and 21 patients who received panitumumab were analyzed. Cetuximab caused hypomagnesemia in more than half of the patients, among whom 4 had severity up to grade 2/3 level, whereas panitumumab induced hypomagnesemia in 90% of the patients with severity up to grade 2 level occurring in 38% of the patients. Intravenous magnesium supplementation on the day of anti-EGFR treatment did not always adequately control the magnesium wasting in these patients. Often treatments with these agents had to be interrupted or terminated as a result of severe electrolyte depletion despite supplementation. Taking into consideration the mechanism of magnesium wasting from the kidney and the magnesium transport process in the gut, intravenous magnesium infusion coupled with oral supplementation with more tolerant oral magnesium products may help improve the treatment outcome in these patients. Surprisingly, more than half of these patients showed significant decreases in their albumin levels, which were correlated with the initiation or discontinuation of anti-EGFR therapy. The underlying mechanism of this decrease in albumin level is not known. The increased likelihood of poor outcomes such as mortality, morbidity and prolonged hospital stay in acutely ill patients with hypoalbuminemia is well recognized. Moreover, the maintenance of adequate serum albumin levels in these patients receiving anti-EGFR therapy may play an important role in containing some of the adverse effects of concurrently administered chemotherapeutic agents.