The initial purpose of this study was to ascertain the species abundance of snakes inhabiting a 371 ha reconstructed marsh, the Marais Temps Clair Conservation Area in St. Charles County, Missouri. This flood-prone refuge is surrounded by agricultural lands and is upstream from the confluence of the Mississippi and Missouri rivers. Only eight species inhabit the study area. The abundance of all eight species declined dramatically after major flooding of both rivers in 1993. Subsequent major flooding in 1995 had little additional effect. The proportion of pre-flood resident species at our site to the number of non-resident species known to occur in the surrounding county was significantly lower than similar ratios at other conservation areas in nearby Missouri and Illinois. Resident species at our site were more likely to be semi-aquatic and arboreal than species found in the surrounding county, and post-flood survivors were significantly larger than pre-flood individuals. We attribute two mechanisms for the unexpectedly low species diversity: (1) the effects of major flooding, and (2) the reduction of immigration access from the area surrounding the study area following Euro-American settlement. We recommend that isolated flood-prone refuges should be provided with internal or peripheral islands that would mitigate the effect of flooding upon local species diversity by serving as a “lifeboat” to increase survivorship of resident populations and as a “landfall” for flood-borne individuals swept downstream from upstream sources.