We present the case of a 55-year-old female patient with metamizole-induced agranulocytosis after total knee arthroplasty, leading to septic periprosthetic joint infections (PJIs). Owing to metamizole-induced agranulocytosis, the synovial leukocyte count was negative. Here, we discuss the diagnostic challenges evolving from sepsis and neutropenia in patients with suspected PJIs. We suggest an urgent surgical approach, mainly focusing on the clinical presentation preoperatively. Later, our patient developed candidemia and periprosthetic tissue samples were positive for Candida albicans. For fungal PJIs, long-term follow-up studies are lacking and therapeutic recommendations differ. Here, we present our therapeutic approach, including staged revision and 12 weeks of systemic antifungal therapy, and discuss recent findings regarding the therapy of fungal PJIs.