After trying his luck at last year's Indianapolis 500, the 36-year-old Spaniard will take a spin around another iconic US venue at Daytona International Speedway, best known for hosting NASCAR's prestigious Daytona 500.
Alonso's participation is part of the McLaren driver's broader quest to complete the "Triple Crown" of motor-racing -- wins at the Formula One Monaco Grand Prix, the Indy500 and Le Mans.
This weekend he will be racing a prototype Ligier JS P217 for the United Autosports team, which is owned by his F1 boss Zak Brown.
Team-mates will include Phil Hanson and Lando Norris, a long-time reserve driver at McLaren. Alonso meanwhile is looking forward to being pushed out of his comfort zone in the gruelling day-night race.
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"I know it could be useful for the future, my first time in a prototype car, and some nice experience I'm sure in traffic, night racing," Alonso said.
Alonso served notice of his ability to adapt to new environments at Indianapolis last year, when he confounded sceptics by leading for 27 laps before withdrawing 20 laps from the finish due to engine failure.
The Spaniard got his first taste of endurance racing last year in Bahrain, when he took part in tests for Toyota.
He told reporters on Thursday he remains optimistic about racing in Le Mans, rating his chances as 50-50.
"It's no secret that I would like to race at Le Mans in the future. If it's this year or not this year, I'm still not 100 percent sure," Alonso said.
"It could happen, yes. (It's) 50/50. There are many things that you need to put together to make it happen, and we are trying to do everything we can.
"Hopefully, yes is the answer, but whether it will be yes or no, you will all know at the same time as I do.