Mike Brown has been ruled out of England's Six Nations clash with Ireland on 1 March having failed to recover from a concussion.
The Harlequins full-back suffered the injury in the 19th minute of the 47-17 win over Italy on 14 February.
Brown failed the third stage of a fitness protocol implemented following head injuries when he awoke with a mild headache on Wednesday morning.
Alex Goode is expected to start in his place in what will be his first Test starting appearance since 2013.
Coach Stuart Lancaster said: "Mike and our medical staff have been diligent during every step of the graduated return to play protocol and they will continue to work to get him back to full health. The most important thing is Mike's welfare.
"We are of course disappointed to lose him but Alex is an experienced international and in great form for Saracens."