Max Verstappen and Pierre Gasly will start at the back of the grid for the Italian Grand Prix after taking on the new Spec 4 Honda power unit.
Honda has opted to take the penalties at the Monza circuit, likely in order to help better prepare for more favourable circuits such as Singapore and Mexico.
The Formula 1 technical regulations only allow up to three power unit changes within a season before grid penalties are handed out.
Alexander Albon and Daniil Kvyat recently took on the Spec 4 unit at the previous race in Belgium and also started the race at the back of the field.
Gasly has taken on the power unit usage from Albon's former car due to their respective team swaps.
"We now go from one classic track to another, from Spa to Monza for the Italian Grand Prix, which is the last race in Europe this year," said Honda chief Toyoharu Tanabe.
"It is one of the highlights of the season and also the home race for one of our teams, Scuderia Toro Rosso.
"From a PU point of view, the main development is that we plan to run the Spec 4 PU with all four drivers for the first time, after just Albon and Kvyat ran it in Belgium.
"For their first race with Spec 4, Gasly and Verstappen will therefore take grid penalties and start from the back of grid, but we believe they can still race strongly on Sunday.
"We gathered useful data in Spa, which we have used to make changes to PU settings and calibration in preparation for this race.
"We will try to maximize the potential of Spec 4 and hope to get another positive result, maintaining the momentum we gained in Spa."