Police said at 2.45pm on Saturday (March 31) a large group of motorcyclists was travelling west on the A27 Pevensey bypass, west of Walls End roundabout, when several of the group collided.
One of the riders, a 51-year-old man from Westcliff-on-Sea, Essex, sustained a serious head injury and less serious chest and back injuries, and was taken to the Royal Sussex County Hospital, in Brighton, where his condition is assessed as potentially life-changing, police said.
Two other riders came off their motorcycles and one sustained slight injury for which he did not require hospital treatment. The other man was unhurt, according to a police spokesman.
Anyone who saw what happened or who saw the group in the moments leading up to the collision, is asked to contact the police online or by calling 101, quoting Operation Mercury.