The bus, carrying 21 people, was en route to Bhirahawa from Pokhara when it skidded off the Siddhartha Highway in Palpa district and fell into the Bhalukhola river at around 2 am (local time).
All the deceased are men and their identities are yet to be established, Palpa DSP Shiva Shrestha said.
"The bus might have lost control of the vehicle after the driver dozed off at the steering wheel leading to the accident," he said.
At least seven persons, including two women, were injured in the accident. Of them, four are undergoing treatment at Mission Hospital, Bhusaldanda while others are being treated at Lumbini Teaching Hospital of the district, The Himalayan Times reported.
Locals, police and army personnel are carrying out the rescue operation at the site of the accident.