The Argentine had been scheduled to play in the January 4-11 Brisbane event, ahead of defending his title in the Sydney International from January 11-17 in the lead-up to the Australian Open.
But Brisbane International officials said del Potro "was forced to withdraw with a persistent left wrist injury".
After winning the US Open in 2009, Del Potro's career was hampered by surgery on his right wrist in 2010 before he fought his way back into the top 10 again.
Pain in his left wrist first flared up at the Australian Open last January.
He retired from his opening match in Dubai the following month and then withdrew from tournaments in Indian Wells and Miami, undergoing surgery in late March. He has not played since.
Del Potro's withdrawal from Brisbane follows that of 2014 US Open winner Marin Cilic who was forced to pull out earlier this week with a shoulder injury.
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