Human natural killer (NK) cells are lymphocytes that destroy tumor cells, virally infected cells, and antibody-coated cells. Tetrabromobisphenol A (TBBPA) is used both as a reactive and an additive flame retardant in a variety of materials and appears to contaminate the environment. TBBPA has been found in human blood samples and if it interferes with NK cell function, this could increase risk of tumor development and/or viral infection. This study examines the effects of exposure to various concentrations of TBBPA for 24 hr, 48 hr, and 6 d on the lytic function, tumor-target-binding function, and ATP levels of NK cells. These same parameters were also monitored in NK cells that were exposed to TBBPA for 1 hr followed by 24 hr, 48 hr, and 6 d in TBBPA-free media. A 24 hr exposure of NK cells to 5 μM TBBPA caused a greater than 95% decrease in NK lytic function, a 70% decrease in binding function, and a 34% decrease in ATP levels in NK cells. Exposure to 2.5 μM TBBPA for 24 hr decreased lytic function by 76%, binding function by 20%, and had no effect on ATP levels. Exposure of NK cells to 5 μM TBBPA for 1 hr followed by 24 hr in TBBPA-free media caused a progressive and persistent loss of lytic function (41%) while not affecting either binding ability or ATP levels. The results indicate that TBBPA exposures decrease the lytic function of human NK cells and that an initial brief (1 hr) exposure can cause a progressive loss of function. Additionally, the data also indicate that TBBPA-induced loss of NK lytic function can occur at concentration of TBBPA that do not affect target-binding ability and ATP levels of NK cells.