Nancy Kissel was convicted in 2005 of giving her husband a milkshake laced with sedatives before fatally beating the wealthy banker on the head with a metal ornament during an argument in 2003.
Kissel said she did it in self-defense. Prosecutors argued she planned the attack in the couple's luxury apartment.
The three-judge court rejected Kissel's request, but the 44-year-old Minnesota native's attorney said he would ask the Court of Final Appeal to hear her case.
The case made headlines worldwide because of allegations of drug abuse, kinky sex and adultery in the wealthy world of expats in this Asian financial center.
Defense attorney Simon Clarke said he was "very disappointed" with Monday's decision, but added that he expected "a better hearing at the Court of Final Appeal."
Kissel said her 40-year-old husband, Robert, an investment banker for Merrill Lynch, was an erratic whiskey-swilling workaholic who also snorted cocaine and forced her to have sex.
She testified that she killed him as he was threatening her with a baseball bat in a quarrel.
During the appeal hearings, Kissel's defense lawyer said the woman suffered an abnormality of mind that substantially impaired her self-control.
But prosecutors argued that Kissel was a cold-blooded, scheming woman who plotted to kill her husband.
They said Robert Kissel of New York had been angry about his wife's affair with a repairman who worked on the couple's vacation home in Vermont. He had planned to seek a divorce just before she killed him, they said.
Robert Kissel's estate was worth $18 million in life insurance, stocks and properties, prosecutors said.