The 45-year-old Sheridan plays vamp Edie Britt on the comedy-drama about domestic life on Wisteria Lane. The network did not say Wednesday when Sheridan's role would end.
Her departure was first made public by TV Guide magazine.
A call to Sheridan's publicist was not immediately returned.
"Desperate Housewives," a top 20 show and one of ABC's most successful series, stars Teri Hatcher, Felicity Huffman, Marcia Cross and Eva Longoria Parker.
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