Lawrence, who has been in fine form for Bath and had been expected to be a certain starter in midfield for Steve Borthwick, has been forced to withdraw from a pre-tournament camp in Girona.
Sale hooker Luke Cowan-Dickie and Harlequins back Oscar Beard have also withdrawn from the squad due to injury, though Beard will travel to Spain to progress through the return-to-play protocols after concussion.
Uncapped Bath backs Max Ojomoh and Will Muir have been called up to Borthwick’s 36-player squad alongside Newcastle hooker Jamie Blamire, who won his last cap in August.
Lawrence was used mainly from the bench during England’s World Cup campaign, but had been set to again take on a starting role in the absence of Manu Tuilagi.
He has impressed at both inside and, particularly, outside centre for high-flying Bath, combining well with Scotland’s Finn Russell and the rest of an eye-catching backline.
His absence would leave England short of power-carrying options in midfield, with Exeter’s Henry Slade and the uncapped Fraser Dingwall the other two specialist centres originally named.
Dingwall’s Northampton teammate Tommy Freeman has also been utilised at 13 this year, while the versatile Elliot Daly could also be an option.
Cowan-Dickie, meanwhile, had been due to compete with Theo Dan for the back-up hooker slot behind new captain Jamie George.
England open their Six Nations campaign in Rome on Saturday 3 February. They will fly directly to the Italian capital after their training camp in Spain concludes next Thursday.