In a 2-1 vote, the court said Apple broke antitrust laws when it entered an e-book market which was then dominated by Amazon.
Circuit Judge Debra Ann Livingston said the price-fixing meant Apple "found an easy path to opening its iBookstore".
"While we want to put this behind us, the case is about principles and values," Apple said.
"We know we did nothing wrong back in 2010 and are assessing next steps."
The US Justice Department said publishers involved in the conspiracy included Hachette, HarperCollins, Penguin, and Simon & Schuster.
The department said that the price collusion meant that some e-book prices rose from $9.99 to up to $14.99.
However, in a dissenting opinion, the judge who upheld Apple's appeal said the company's entry into the e-book market was pro-competitive as it challenged Amazon, which controlled about 90% of the sector.
"Apple took steps to compete with a monopolist and open the market to more entrants, generating only minor competitive restraints in the process," Judge Dennis Jacobs wrote.
The appeal followed a 2013 decision by US District Judge Denise Cote in Manhattan that Apple played a "central role" in a conspiracy with publishers to eliminate retail price competition and raise e-book prices.
The Justice Department and 33 states and territories originally sued Apple and five publishers. The publishers all settled and signed consent decrees prohibiting them from restricting e-book retailers' ability to set prices.
Apple conspired with publishers to fix the prices of electronic books, a US federal appeals court has ruled.