The Sea Lamprey Petromyzon marinus control program in the Laurentian Great Lakes is one of the longest-running and most successful invasive species suppression programs in the world. Although several techniques are used to suppress Sea Lamprey, the control program relies heavily on regular application of lampricide to kill stream-dwelling larvae. The COVID-19 pandemic disrupted lampricide application from 2020 to 2022, which provided a unique opportunity to test how Sea Lamprey populations and wound counts on fishes would respond. We evaluated the consequences of decreased control effort at a basin-wide level using standard control program metrics and through a focused analysis of multispecies wounding in Lake Ontario, which experienced the greatest disruption in Sea Lamprey control. The reduction in control effort corresponded to increased basin-wide adult Sea Lamprey abundance but was only weakly associated with Lake Trout Salvelinus namaycush wounding. However, the novel multispecies wounding rate metric calculated for Lake Ontario increased and was consistent with observations by anglers and managers regarding a sharp increase in Sea Lamprey abundance following reduced effort. Ultimately, our research highlights that consistent treatment is critically important for preventing damage stemming from Sea Lamprey and that reductions in suppression could quickly lead to a resurgence in abundance.