Virgin Trains has cancelled all West Coast mainline services on Monday and Tuesday because of a planned strike by Network Rail workers.
It will also only run a very limited service on the East Coast line on Bank Holiday Monday and Tuesday if the action goes ahead.
Virgin, which runs services on the major routes between London and Scotland, said if the strike goes ahead some tickets may be used on other days.
Virgin Train East Coast said: “Due to this action, we strongly recommend customers, whose travel plans are flexible, travel on Sunday or later in the week when existing tickets will be valid.”
Thousands of signallers, maintenance staff and station workers are due to walk out for 24 hours from 5pm on Monday in a row over pay and jobs.
Widespread cancellations are also expected across other operators including CrossCountry Trains, Chiltern Railways, Arriva Trains Wales, First Great Western and ScotRail.
Passengers are being advised not to travel unless “absolutely necessary”. The two sides are continuing to hold talks at the conciliation service Acas.