The back-row only returned from a three-month spell on the sidelines with a knee injury in the Premiership victory against Wasps last weekend and suffered another cruel setback at the Liberty Stadium.
Vunipola was replaced at half-time in the Champions Cup clash, which ended 15-15, and Saracens on Sunday revealed that an X-ray showed he had fractured his forearm, just three weeks before England start the defence of their Six Nations title against Italy in Rome.
"Billy is due to see a specialist later this week, when a timeframe for recovery may be defined," said a Saracens spokesman.
"But until that time Saracens will make no further comment. Saracens will issue a further statement once Billy has seen a specialist."
The luckless Vunipola had earlier given a strong indication that he was facing another frustrating period out of the game.
He posted on Instagram: "One of these days I might actually be able to play more than 2 games without breaking (no pun intended).
"I said it before and I'll say again. God has a plan for me, it's just hard having to be patient!"
The loss of the Australia-born powerhouse will serve as huge blow to England head coach Eddie Jones, who must have been hugely encouraged by his performance against Wasps.
Vunipola said after his comeback at the Ricoh Arena: "It means a great deal [to come back] and I feel I'll be better for it next week and hopefully, if I can keep going like this, I'll be back to where I was in no time.
"It can be frustrating being injured but there can be higher powers at work. It taught me a huge lesson about looking after myself better in terms of recovery and sleep. I thought I did that better this time. Whatever runs for me, I'll just try to smash it.
"If I can convince Eddie I am in the right shape and playing well enough to be picked in his squad, then great. I want to play for England as much as I can and I have missed it but right now my biggest focus is playing well for Saracens and hopefully transferring that on to the pitch at Twickenham."
He will also be sorely missed by European champions Sarries, who are in great danger of missing out on the Champions Cup quarter-finals after they were held by the Ospreys.
Photo Getty Images. Caption: Saracens and England's Billy Vunipola