Leader Leanne Wood said a "strong opposition" would be in the national interest if First Minister Carwyn Jones had a majority as a result.
The Welsh Government has denied rumours that it may appoint former Plaid leader Lord Elis-Thomas.
Labour won 29 seats at the May election, two short of a majority.
It already has one minister from outside the party - Lib Dem AM Kirsty Williams, who is education secretary.
Plaid had formed the so-called "compact" with Labour in May following the deadlocked vote between Labour leader Mr Jones and Ms Wood over who should be first minister.
Lord Elis-Thomas left Plaid Cymru in October to sit as an independent AM, claiming the party was not "serious" about supporting the Labour administration.
Plaid came to a deal with Labour to back the Welsh budget the same month.
In a blog post on the Plaid website, Ms Wood said that "co-operation hasn't happened by accident, and it cannot be taken for granted.
"It is based on the existing arithmetic of the assembly.
"If the arithmetic of the assembly changes, for example if any new assembly member is brought into the government from outside, then Wales will have a majority government," she said.
"In that case, the Welsh national interest would best be served by a strong opposition to Labour from Plaid Cymru.
"Under those circumstances, the compact would come to an end," she added.
A Welsh Government source has denied Lord Elis-Thomas is being offered a ministerial job.
A spokesman for the Welsh Conservatives said they "stand ready to show Plaid Cymru the true meaning of strong opposition should it decide to unravel itself from Labour's cosy embrace".
"Plaid Cymru's so-called 'compact' with the Welsh Government is little more than a sop, which is evident to all but Plaid Cymru," the spokesman said.
"In pandering to the whims of Carwyn Jones, Plaid is perpetuating a saga of mediocrity now spanning nearly two decades."
Plaid Cymru has warned its co-operation deal with Labour will end if it appoints another AM from outside the party to the Welsh Government.