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Anuric hemodialyzed end-stage renal disease patients are prone to multiple complications and comorbidities and are therefore often treated with various medications. Adverse drug reactions and risk factors leading to them can be difficult to discern in such polymedicated patients. Most problems regarding low phosphate levels are frequently underdiagnosed in clinical practice and sometimes overlooked in these regularly hyperphosphatemic patients. Hemodialysis vascular accesses are frequently subject to infections and therefore require adapted antibiotic treatments. We report a case of an occult severe multifactorial hypophosphatemia in an anuric hemodialyzed patient with multiple comorbidities who required two hospitalizations for encephalopathy, seizures, and cardiac failure. Retrospective analysis of the medical record revealed several underlying causes of hypophosphatemia, as well as undetected risk factors for adverse drug reactions related to cephalosporins. A global approach to these concerns in routine clinical practice would raise awareness of often disregarded issues related to hypophosphatemia and drug prescription in these patients.