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The Burmese python (Python molurus bivittatus) is established in Everglades National Park and neighboring areas in south Florida. Beyond its substantial ecological impacts to native fauna in south Florida, concerns have been raised as to its potential to occupy other parts of the USA, even as far north as Washington, DC. During a recent period of cold weather, seven of nine captive Burmese pythons held in outdoor pens at our facility in north-central Florida died, or would have died absent our intervention. This cold-induced mortality occurred despite the presence of refugia with heat sources. Our findings cast doubt on the ability of free-ranging Burmese pythons to establish and persist beyond the subtropical environment of south Florida.