Paying his first visit to Afghanistan as Pentagon chief, Mattis met with President Ashraf Ghani and other officials and US military commanders.
"We're under no illusions about the challenges associated with this mission," he said at a press conference in Kabul with General John Nicholson, US commander of NATO forces in Afghanistan.
"2017 is going to be another tough year for the valiant Afghan security forces and the international troops who have stood, and will continue to stand, shoulder-to-shoulder with Afghanistan against terrorism," he said.
"It shows why we stand with the people of this country against such heinous acts perpetrated by ... This barbaric enemy," Mattis said.
Nicholson recently called for "a few thousand" more troops but Mattis would not be drawn on extra forces to help battle the resurgent militants, who are gearing up for the spring fighting season.
The Pentagon chief, who served in Afghanistan, is compiling an assessment for President Donald Trump on the brutal and seemingly intractable conflict.
"As you know, President Trump has directed a review of our policy in Afghanistan as the new administration takes hold in Washington. This dictates an ongoing dialogue with Afghanistan's leadership and that's why I came here," he said.
The resignations, along with the announcement of a corps commanders reshuffle, followed fury over the Taliban assault on an army base outside the northern city of Mazar-i-Sharif.
Gunmen in soldiers' uniforms and armed with suicide vests entered the base in army trucks and opened fire at unarmed troops in one of the deadliest-ever Taliban attacks on an Afghan military target.
Afghan authorities have so far ignored calls to break down the official toll of more than 100 soldiers killed or wounded. Some local officials have put the number of dead alone as high as 130.
Up to 10 army personnel are being questioned as suspects, a military spokesman attached to the base said, amid fears it could have been an insider attack.
At least four of them had valid passes to the base and had previously trained there, a security source told AFP.
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