Sulfur and its derivatives, including sulfur-containing inorganic and organic compounds, are known to possess broad-spectrum antibacterial properties and have been efficiently used in treating dermatological disorders and plant diseases. [2-4] However, the bulk quantities required for application and high hydrophobicity of sulfur have limited its use. [5] As such, the development of synthetic nanotechnology has provided an exciting new avenue for the use of sulfur. Recent studies have indicated that inorganic sulfur in the form of nanoscale metal sulfides, such as molybdenum disulfide (MoS 2), [6] copper sulfide (CuS), [7] and iron sulfide (FeS), [8] exhibits high antibacterial activity. Thus, fabricating nanoscale metal sulfides may be a promising way in which to improve the antibacterial efficacy of sulfur. Nevertheless, due to the variable valences and abundant forms of sulfur, the exact antibacterial mechanism of metal sulfides has not been fully elucidated. For example, the strong antibacterial effects of CuS nanodots are reported to be the result of Cu 2+ release, [9] whereas MoS 2 nanomaterials are thought to exert bactericidal activity by working as β-lactamase inhibitors. [10] In addition, we previously found that polysulfides released from nano-iron sulfides exhibit high antibacterial effects. [11] Thus, the antibacterial mechanisms of metal sulfides need to be Recent progress in nanotechnology and the ancient use of sulfur in treating dermatological disorders have promoted the development of nano-sulfides for antimicrobial applications. However, the variable valences and abundant forms of nano-sulfides have complicated investigations on their antibacterial activity. Here, carbon nanospheres (CNSs) with decoration of ultrasmall FeS 2 nanoparticles (CNSs@FeS 2) is synthesized, and their antibacterial ability and mechanism are explored. The CNSs@FeS 2 released Fe 2+ and sulfur ions simultaneously through dissolution and disproportionation. In vitro study indicated that the released Fe 2+ killed bacteria by increasing the oxidative state of bacterial surfaces and intracellular molecules. Importantly, the released sulfur exhibited a protective effect on Fe 2+ , ensuring the stable existence of Fe 2+ to continuously combat bacteria. Moreover, the carbon shells of CNSs@FeS 2 not only prevented the aggregation of FeS 2 but also accelerated the release of Fe 2+ through photothermal effects to achieve synergistic hyperthermia/Fe 2+ therapy. In vivo experiments indicated that treatment with CNSs@FeS 2 resulted in a marked reduction in bacterial number and improvement in survival in an acute peritonitis mouse model, and antibacterial wound experiments demonstrated high efficacy of CNSs@FeS 2-enabled synergistic hyperthermia/Fe 2+ therapy. Thus, this study clarifies the antibacterial mechanism of FeS 2 and offers a synergetic therapeutic platform with laser-mediated Fe 2+ release for antibacterial applications.