AbstractAvian influenza A (H5N1) virus infection can cause severe pneumonia, but the development of acute respiratory distress syndrome (ARDS) and hemophagocytic lymphohistiocytosis (HLH) syndrome is rare. We report a case of rapidly progressive and fatal H5N1 infection that was complicated by HLH and multiorgan failure. The purpose is to highlight the potential for H5N1 infection to trigger life-threatening complications, including ARDS and HLH syndrome. Early recognition and aggressive treatment may improve survival in these critically ill patients.