In addition, in January 2004, he announced that his government would hold a series of rallies around the country and at its embassies abroad, demanding that Chile return to Bolivia a stretch of seacoast that the country lost in 1879 after the end of the War of the Pacific. He did not resign, but he did withdraw his support for Sánchez de Lozada five days before the latter's resignation, saying: 'I cannot continue to support the situation we are living through.' It also placed him at the center of extreme political pressures from both internal Bolivian and external foreign interests regarding the use of Bolivia's rates and the property of the gas reserves for the Bolivian state.

As the gas conflict escalated, Mesa ended discontent with the government's heavy-handed repression of the protests, which would leave over 60 people dead during September and October 2003.