In March 1863, the regiment was transferred to Grand Gulf, Mississippi, where the regiment built fortifications. The next month, the regiment was part of an observation force sent across the Mississippi River into Louisiana. After returning from Louisiana, the regiment was stationed at Grand Gulf, and did not participate in the Battle of Port Gibson on May 1. On May 3, the regiment was part of a rear guard that protected the Confederate retreat from Grand Gulf. At the Battle of Champion Hill on May 16, the 2nd Missouri Infantry, along with the rest of the First Missouri Brigade (now commanded by Cockrell) plugged a gap in the Confederate line. Later in the afternoon, Cockrell's brigade responded with a counterattack, driving Union troops back and recapturing the cannons of Waddell's Alabama Battery, which had been captured earlier in the fighting. The attackers suffered heavy casualties in the charge, one member of Cockrell's brigade later wrote that "blood ran in a stream, as water would have done." The charge gained momentum, eventually reaching the top of Champion Hill, a prominent landmark on the battlefield. Eventually, Union reinforcements arrived, blunting the Confederate charge and forcing the attackers to retreat. At Champion Hill, the 2nd Missouri Infantry suffered casualties of 10 men killed, 35 wounded, and 38 missing, for a total of 83.