Head coach Vern Cotter last week named the South Africa-born tighthead in his 37-man squad for the Championship.
But the 15-cap forward - tipped for a British and Irish Lions call-up - has been forced to withdraw after aggravating a neck injury while on duty for club side Edinburgh last week.
His chances of joining Warren Gatland's touring party for the summer trip to New Zealand may also be thrown into doubt after Scottish Rugby announced the 30-year-old will meet with a specialist to decide whether surgery is required.
In a statement, a spokesman for the Dark Blues said: "An MRI scan on Wednesday at Spire Murrayfield Hospital revealed that the tighthead prop damaged an intervertebral disc in his neck during a significant collision in his club's European Challenge Cup win over Harlequins at the Twickenham Stoop on Saturday (14 January).
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"Nel will now have a second specialist assessment at Spire this Monday to consider his programme of recovery, including whether corrective surgery is required."
Nel has already missed two-a-half months worth of action - including Scotland's November Test clashes with Australia, Argentina and Georgia - after suffering an earlier neck injury while playing for Edinburgh.
He lasted just 26 minutes of his return to action against Quins before being helped off after a head knock which has caused his latest setback.
Cotter will now have to turn to Glasgow's Zander Fagerson to deputise for his star prop.
However, the 21-year-old is highly rated by the out-going Scotland coach and started all three Autumn internationals in Nel's original absence.
