World number four Del Potro is still sidelined with a right knee injury sustained in Shanghai last month.
Nishikori will join Novak Djokovic, Rafael Nadal, Roger Federer, Alexander Zverev, Kevin Anderson, Marin Cilic and Dominic Thiem at the elite eight-player event.
"It's frustrating for me not to be able to compete in London," Del Potro, who last played in the event in 2013 since when he has been plagued by injuries, said in an ATP statement.
"It's a very special tournament and I've tried everything possible to get my knee better. The rehabilitation is making good progress, but I need more time.
"Of course, it's disappointing for me right now, but I had a very good season overall."
Nishikori will be making his fourth appearance at London's O2 Arena where he reached the semi-finals in 2014 and 2016.
"First of all I want to wish @delpotrojuan a speedy recovery," the 28-year-old said on Twitter. "He had an amazing year. Second I am very excited to join the London field.
"I started my year with challengers and missed the Aussie Open and Indian Wells. Very proud of the way the year turned out."
(Reporting by Martyn Herman, editing by Ed Osmond)
