Guillen was suspended for 15 days on Thursday by the Commissioner's Office for violation of Major League Baseball's Drug Prevention and Treatment Program.
The suspension will start at the beginning of the 2008 season.
"We signed Jose knowing that was a possibility," Royals general manager Dayton Moore said in a statement. "While my initial reaction is one of disappointment, I am thoroughly convinced that Jose will put this behind him and we collectively support him as he begins a new chapter in his baseball life as a member of the Kansas City Royals. As I've stated on numerous occasions, we went into this winter seeking an impact bat in the middle of our lineup and I know we've acquired such a bat in Jose Guillen."
Also suspended for 15 days was outfielder Jay Gibbons of the Baltimore Orioles.
The Royals had announced just Thursday morning that Guillen had been signed to a three-year contract, reported to be for $36 million. Scant hours later, the suspension came down from the Commissioner's Office.
Guillen was pursued by the Royals even though he had been linked to the alleged purchase of human growth hormone by the San Francisco Chronicle. The drug was banned by Major League Baseball in January 2005.
On Wednesday, ESPN reported that the Major League Baseball Players Association was negotiating with MLB over a 10- or 15-day suspension for Guillen. MLB's Rob Manfred responded that he had talked to Guillen, the matter was under investigation, and that MLB does not negotiate punishment.
Guillen was signed to provide sock in the middle of the Royals' lineup, offering protection for their young hitters. He had 23 home runs last season for the Seattle Mariners.
The Royals have been notoriously slow getting out of the gate in recent Aprils. Now, they'll start the 2008 season without their just-signed slugger.
Dick Kaegel is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.