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Sin Nombre virus (SNV) is a zoonotic virus that is highly pathogenic to humans. The deer mouse,Peromyscus maniculatus, is the primary host of SNV, and SNV prevalence inP. maniculatusis an important indicator of human disease risk. Because the California Channel Islands contain permanent human settlements, receive hundreds of thousands of visitors each year, and can have extremely high densities ofP. maniculatus, surveillance for SNV in islandP. maniculatusis important for understanding the human risk of zoonotic disease. Despite the importance of surveillance on these heavily utilized islands, SNV prevalence (i.e. the proportion ofP. maniculatusthat test positive to antibodies to SNV) has not been examined in the last 13–27 years. We present data on 1,610 mice sampled for four consecutive years (2014–2017) on five of the California Channel Islands: East Anacapa, Santa Barbara, Santa Catalina, San Nicolas, and San Clemente. Despite historical data indicating SNV‐positive mice on San Clemente and Santa Catalina, we detected no SNV‐positive mice on these islands, suggesting very low prevalence or possible loss of SNV. Islands historically free of SNV (East Anacapa, Santa Barbara, and San Nicolas) remained free of SNV, suggesting that rates of pathogen introduction from other islands and/or the mainland are low. Although continued surveillance is warranted to determine whether SNV establishes on these islands, our work helps inform current human disease risk in these locations and suggests that SNV prevalence on these islands is currently very low.