Courtney Lawes looks set to miss Saints' Challenge Cup quarter-final at Clermont Auvergne after it was confirmed that the England lock will be out for a minimum of four weeks.
Lawes suffered a calf strain during England's Six Nations defeat to Wales in Cardiff.
The lock had to be helped from the field and was sent for an MRI scan on Sunday.
That has revealed that the Saints star will now miss the remainder of the Six Nations.
And he would appear hugely unlikely to travel to France with Saints to take on Clermont Auvergne in exactly five weeks' time (March 31).
He is also set to miss the east midlands derby at Welford Road on March 22, though he would have probably been given that game off anyway as it comes just six days after England conclude their Six Nations campaign, at home to Scotland.
Lawes will now be back at Franklin's Gardens as he continues his rehabilitation.
It is the second injury blow in as many days with the news that Dylan Hartley will go for surgery on a knee problem on Tuesday.
Hartley, who has not played since starting in Saints' win at Worcester Warriors on December 21, is also set to be out for a minimum of four weeks.
Saints boss Chris Boyd said: "Dylan went to see the surgeon and they felt in conjunction with our medical people the progress was a bit slow.
"He's going to have a surgical procedure on Tuesday to open it up and see what's causing the knee to be grumbly.
"Depending on what they find, it will depend on how long his rehab will be.
"If it went outstandingly well, he could be playing in four weeks but if it's something a bit more problematic it might be a bit longer.
"We won't really know what time-frame it is until they have a look and then it will depend on his rehab.
"We certainly won't be putting any pressure on him. He'll play as soon as he can."