High traffic volume is one of the main contributors to wildlife-vehicle collision (WVC) and wildlife mortality on roads. Government shelter-in-place (SIP) orders have been used to help mitigate the spread of COVID-19, resulting in unprecedented reductions in global traffic volumes. Using traffic and collision data from four US states (California, Idaho, Maine, and Washington), we investigated changes in total WVC, following the state and local SIP orders. From mid-March to mid-April 2020, these orders have resulted in up to 71%, 63%, 73%, and 72% reduction in driving, as measured by vehicle miles traveled (VMT), in CA, ID, ME, and WA respectively. The daily WVC rates from the 4 weeks prior to SIP orders going into effect, to the 4 weeks after, declined 34%, with 21, 36, 44, and 33% declines for CA, ID, ME, and WA, respectively. For mountain lions ( Puma concolor) in CA, there was a 58% decline in mortality during the traffic reduction. The changes in WVC from 1 month pre-SIP orders to 1 month post-order only occurred in 2020 and not 2015, 2016, 2017, 2018, or 2019, suggesting that the reductions were associated with the reductions in traffic. The measured declines in WVC reversed in ME and WA during May, June and July 2020, paralleling reversals in traffic volumes. A 34% reduction in WVC would potentially equate to 10s of millions fewer vertebrates killed on US roadways during one month of traffic reduction, representing an unintentional conservation action unprecedented in modern times.