Many Ca² channel proteins have been detected in mammalian sperm, but only the four CATSPER channels have been clearly shown to be required for male fertility. Ca² entry through the principal piece-localized CATSPER channels has been implicated in the activation of hyperactivated motility. In the present study, we show that the Ca² entry also triggers a tail-to-head Ca² propagation in the mouse sperm. When activated with 8-Br-cAMP, 8-Br-cGMP, or alkaline depolarization, a CATSPER-dependent increase in intracellular Ca² concentration starts in the principal piece, propagates through the midpiece, and reaches the head in a few seconds. The Ca² propagation through the midpiece leads to a Ca² -dependent increase in NADH fluorescence. In addition, CatSper1-mutant sperm have lower intracellular ATP levels than wild-type sperm. Thus, a Ca² influx in the principal piece through CATSPER channels can not only initiate hyperactivated motility, but can also trigger a tail-to-head Ca² propagation that leads to an increase in [NADH] and may regulate ATP homeostasis.