The dog's owners, a man and a woman, were arrested and could face charges including drug possession and animal cruelty, according to the Irvine Police Department.
The incident began with a "consensual" encounter between the couple and police on Wednesday outside a Walmart, department spokesman Kyle Oldoerp said.
After officers discovered fentanyl in their car, the two were arrested, he said.
"Then the female said, 'Oh, I think my dog is overdosing,' " Oldoerp told the Los Angeles Times on Saturday (local time).
"She knew the symptoms because it was the second time the dog had overdosed."
He said it wasn't immediately clear how the dog would have been exposed to the drug, which is up to 50 times more powerful than heroin.
A dose as small as two milligrams can be fatal to a human, though dogs are less sensitive to the drug, according to the Times.
"If they're using drugs in their car, we can only speculate," Oldoerp said.
At the station, officers administered overdose-reversing naloxone to the dog, which made a "pretty quick" turnaround, Oldoerp said.
The man and woman were not identified.
Authorities will hold on to the puppy until there is a hearing to determine whether to give the dog back to its owners, the Times reported.