Nadal made his return from a three-month lay-off but fell to a 4-6, 6-3, 6-4 loss.
The Spaniard is using the exhibition event in Abu Dhabi to build his fitness and to help with the rehabilitation process following ankle surgery.
And he will have been thankful for the lengthy time on court and he looks to get back to top form.
But he will not be happy with letting the one-set lead slip away as he failed to break Anderson’s giant serve in the last two sets.
Nadal’s tournament is not yet over as there is a third-placed play-off tomorrow.
The world No 2 will face the loser of Novak Djokovic vs Karen Khachanov.
It is unlikely Djokovic will lose to his Russian opponent so a rematch of the Wimbledon final between him and Anderson could occur in the Middle East.
But if the Serbian is also stunned it could lead to a blockbuster showdown between the top two players in the world.
Meanwhile, Nadal has provided an update on his fitness after training in the Abu Dhabi sunshine.
"Good, going step by step,” he said
"I am not making steps back, just steps forward all the time, taking care of my body after a while without having a chance to be on court and trying to do things slowly.
"It's important for me to protect the body and to avoid tough circumstances.
"I know I have time to be ready for Melbourne at 100 per cent."
Djokovic has won the Mubadala World Tennis Championship on three occasions, once less than Nadal.