Abstract Silver-containing topical agents are used to help prevent infectious complications in wound therapy. Toxicity from topical silver agent exposure was initially reported in 1975 and was clinically characterized by granulocytopenia. Currently, the data regarding potential toxicity associated with silver-impregnated devices are limited. A 23-year-old patient receiving chemotherapy for acute lymphoblastic leukemia presented with necrotizing fasciitis of the abdominal wall and scrotum from a Crohn disease–related psoas-enteric fistula. Surgical debridement of the soft-tissue and abdominal musculature was performed to the peritoneum. Silver-containing foam sponges and wound vacuum-assisted closure were applied directly to the peritoneum 2 weeks after initial debridement. Subsequently, the patient developed leukopenia, and workup revealed the serum silver level was 4 times normal level. Silver-impregnated sponges were discontinued and silver-free sponges and wound vacuum-assisted closure therapy resumed, followed by leukopenia resolution. Silver toxicity associated with routine application of silver-impregnated sponges has not been previously reported.