Tribal officials reported 56 additional confirmed COVID-19 cases that increased the total to nearly 8,100. The death toll rose to 396 as of Friday.
The number of infections is thought to be far higher because many people have not been tested, and studies suggest people can be infected with the virus without feeling sick.
The reservation includes parts of Arizona, New Mexico and Utah.
The lockdown began Friday night and ends at 5 a.m. Monday. All businesses on the Navajo Nation are also required to close during the lockdown.
For most people, the new coronavirus causes mild or moderate symptoms, such as fever and cough that clear up in two to three weeks. For some, especially older adults and people with existing health problems, it can cause more severe illness, including pneumonia, and death. The vast majority of people recover.