More than half of ambulance workers in Wales are staging the biggest strike to date, following a long-running dispute over pay.
It's the largest day of industrial action as previously both unions involved have only taken part in strikes on separate dates.
It comes after the GMB union rejected an offer from the Welsh Government - which saw an extra 3% added to the existing deal.
Welsh Ambulance Service Chief Executive Jason Killens told ITV Wales on Sunday that the service is concerned about the risk to patients during the strike
Members from Unite will strike for three consecutive days from 00:01 on Monday with those from the GMB union walking out for 24 hours from the same time.
The Welsh Government said it was "disappointed" GMB turned down the revised pay offer, saying it was the best offer it could make.
What is the Welsh Government offering NHS workers?
The offer made by the Welsh Government to health unions is a 1.5% pay increase and a one-off payment of 1.5% of a worker's salary.
This is on top of 4.5% already offered workers be backdated to April 2022.
Nathan Holman, GMB Welsh official said, "This is a clear result and members have had their say on the offer.
"We thank the Welsh Government for actually entering talks, but if this is their final offer, it's too low for our members".
During any strike action, emergency services are still available but everyone has been being urged to use the system "sensibly at this difficult time" as services will be running at reduced capacity.
Jason Killens Chief Executive of the Welsh Ambulance said, "We are concerned about the risk of harm to patients tomorrow.
"We've got a 72-hour strike from members of Unite the union and they're also joined in the 24-hour period on Monday by members of the GMB union so with two unions taking strike action, we're likely to see in excess of 50% of our workforce taking industrial action and that's going to cause significant disruption in our ability to respond to patients in a timely way. "
"Members of the public should always call us if they're in doubt about an injury they've got but what I would say they should only call us in a genuinely life-threatening emergency."
The Welsh Government it was working with the service to ensure that life-saving care will still be provided on the day of the strike and that patient "disruption is minimised".
Twenty military personnel in Wales will be paired with managers in clinical roles to drive ambulances during the strikes.
A spokesperson added that it was "vital" members of the public did all they could to help reduce pressure on the service.