Virgin Trains has cancelled all its West Coast mainline services for 25 and 26 May due to a planned strike by Network Rail workers.
And the operator will also run a very limited service on the East Coast line if the action goes ahead.
Signallers, maintenance staff and station workers are due to walk out for 24 hours from 17:00 BST on 25 May in a row over pay and jobs, and Network Rail has advised passengers not to travel unless it is "absolutely necessary".
Other operators including CrossCountry Trains, Chiltern Railways, Arriva Trains Wales, First Great Western and ScotRail are also expected to be hit by the strike action.
Virgin, which runs services on the major routes between London and Scotland, said if the strike went ahead some tickets may be used on other days.
Union claims 'rock solid support'
A Virgin spokesman said customers travelling on Sunday 24 May or Wednesday 27 May were advised to check for disruption before travelling - while others needed to make alternative arrangements.
RMT union general secretary, Mick Cash, said: "We would remind the public that we have been forced into this dispute through a wholly unwarranted attack on safety-critical jobs, pay and working conditions that would seriously undermine the safety of passengers on our railways into the future.
"RMT members are standing up for the principle of a properly staffed and resourced railway where safety comes first and where corners aren't cut to hit budget targets."
He added that the union had "rock solid" support from his members.
Network Rail is taking legal action against the TSSA, another of the unions involved in the industrial action. Its case is due to be heard at the High Court on Thursday 21 May.
Network Rail's chief executive, Mark Carne, said: "We are continuing to talk with the unions and we believe there is a settlement to be had. I sincerely hope we can reach one and my team will be available all week, and into the weekend if necessary, to find a deal to prevent strike action.
"From the start of negotiations we made clear that we want to reward our staff for the incredible job they do, but that any pay rise needs to be linked to smarter, more effective ways of working. We can't bank on the unions calling off the strike, so we are now concluding our contingency plans so passengers can make decisions about their journeys.
"If the strike goes ahead, it's important that people check before travelling and are aware of the special measures put in place by train operators for people who have already booked tickets."