Twelve passengers and three flight attendants were treated for respiratory issues and released by emergency responders at the airport in Kahului, Hawaii, airline spokesman Alex Da Silva said.
A passenger illegally brought the pepper spray on the plane carrying 256 passengers and 10 crew members, but it appears it discharged accidentally, Da Silva said in a statement. The airline could not provide any details about the passenger or why officials believe the release was accidental.
The flight crew of the Boeing 767 declared an emergency to get priority to land at the airport in Hawaii.
Nicholas Andrade said he and his fiancee were trying to take a nap in their seats just behind first class when the problems began.
"I was woken up by someone having a coughing fit. But what I came to find out is that it wasn't one person coughing, it was many people coughing. And then everyone was coughing and then we were coughing. And the flight attendants were covering their faces and passengers started covering their faces," he said.
People had trouble breathing and were shouting.
"People were definitely panicked," he said.
Flight attendants told the affected passengers to move to the back of the plane where the air wasn't bothering people. He said about 40 people stood in the back galley for about a half-hour until the air around their seats improved.
Andrade was among the 12 evaluated by medical professionals after the plane landed. He said he had a headache and felt light-headed. Other passengers had burning and watering eyes.
Transportation Security Administration spokeswoman Lisa Farbstein said in an email that her agency and Maui police are investigating.
She said the canister held about 1.5 ounces (42 grams). The fine for bringing pepper spray onto an airplane can reach $1,960 or higher, Farbstein said.
The airline said the flight was delayed earlier Friday after a teenager in Oakland sent a photo depicting a fake crime scene "featuring a child-sized mannequin" to other passengers' cellphones. The teen and his family were booked for a later flight while officials investigated.
Hawaiian Airlines said the two incidents were not related and the family's baggage had to be located and removed from the plane, causing the delay.