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The comments come less than 10 days before a planned summit between US President Donald Trump and North Korean leader Kim Jong Un, a high-stakes meeting that the US hopes will lead to North Korean nuclear disarmament.
"We can anticipate, at best, a bumpy road to the negotiation," said Mattis, who was speaking alongside South Korean and Japanese defense ministers at the Shangri-La Dialogue, an annual security summit in Singapore that draws government officials and academics from around the world.
"We must maintain a strong collaborative defensive stance so we enable our diplomats to negotiate from a strong position of strength in this critical time," said Mattis.
"We must remain vigilant, and we will continue to implement all UN security council resolutions on North Korea. North Korea will receive relief only when it demonstrates verifiable and irreversible steps to denuclearization," added Mattis.
Trump's announcement follows negotiations between diplomats on both sides of the Pacific, intended to iron out the summit's final agenda.
The issue of denuclearization, long a sticking point between the two countries, remains the most contentious and challenging aspect of any potential deal.
The North Korean regime has historically shown an unwillingness to relinquish its nuclear capabilities, which it views as a guarantee of survival in the face of US intimidation.
Previously, the US has floated the idea of providing the North with economic assistance and sanctions relief should it agree to a timetable for abandoning its nuclear weapons program.
Regional concerns
"We have seen history repeat where North Korea would declare to denuclearize, by portraying itself as a consolatory and forthcoming, only to turn around and avoid all international efforts towards peace," said Onodera.
Concerns have risen among the US' regional allies in recent days that Trump might consider cutting a deal with Kim that would see Pyongyang agreeing to give up its long-range missiles in return for sanctions relief, while being allowed to hold on to its short-range arsenal, leaving Japan and South Korea in the cross hairs.
"In light of how North Korea has behaved in the past, I believe it is important not to reward North Korea solely for agreeing to have a dialogue," said Onodera, who called for the continuing of the US-led pressure campaign on North Korea during the ongoing dialogue with Pyongyang.
"I know that President Trump said that he would not lift sanctions until North Korea agrees to denuclearization and I understand that pressure will remain in place" Onodera said.
'A stabilizing effect'
Addressing Onodera and South Korean Defense Minister Song Young-moo directly, Mattis said security cooperation between the three partners was vital.
"When we consider the unity of purpose among our three democracies, when we consider the combined economic and defense power represented here, we see that our security cooperation is needed more than ever, providing a stabilizing effect in support of our interests for peace, deterrence, and stability," said Mattis.
"I affirm America's ironclad, unwavering security commitment to your people and our mutual security interests," Mattis added, echoing comments he made Saturday, in which he ruled out the prospect of reducing US troops in the region as part of any potential deal with North Korea on June 12.
"If the diplomats can do their job and reduce the threat then of course they (troop reductions) can come up subsequently," said Mattis Saturday. "(But the issue is) not on the table, June 12 ... nor should it be."
CNN's Joshua Berlinger contributed to this report from Singapore.