The Red Devils proved to be too powerful as they cruised to an 86-62 win.
The loss sends Sikeston to the loser's bracket for the 10th straight season. The last time Sikeston was in the winner's bracket was 1995 when they captured the championship in the tournament.
Sikeston (5-7) was simply out-matched from the start as Murphysboro (15-2) never trailed in the contest.
"They're a really quick team and they're probably as good as anybody we've played all season," said Sikeston coach Gregg Holifield. "They shot the ball exceptionally well. They're just a well-rounded team. They have quickness, they can defend, they push the basketball offensively and they can shoot. It was just a real tough first round opponent for us."
The Red Devils led 21-12 after one quarter. Sikeston was able to keep it close for much of the second quarter, trailing just 30-24.
But Murphysboro slapped on a full-court press that turned the game into a one-sided affair.
The Red Devils finished the half on a 17-5 run to take a 47-29 halftime lead.
"They just exploded and I knew they were capable of that with all the scouting reports I had on them," said Holifield. "They can play like that in spurts. They scored 10 points very quickly and put us in a 15-point deficit. There's a lot of talent and a lot of ability on that team."
Sikeston kept the game in respectable range through much of the third quarter as they trailed 56-42, but once again the Red Devils turned it up when they had to as they closed the quarter on a 15-6 run to lead 71-48 heading into the final frame.
Substitutes played most of the fourth quarter for both teams to finish out the game.
"We battled hard and didn't quit," said Holifield. "But against teams like that we have a lot of matchup problems with their size and quickness. It was just a tough game for us."
The high-flying Red Devils were led by Lamont House's 26 points as the 6-foot-2 senior put on a dunking exhibition for the fans.
Steven Schauf followed up with 23 points, including four 3-pointers.
Traveon Loving added 15 points. Point guard Aram Adams had six points with 14 assists to set a new tournament record.
The Red Devils canned 10 3-pointers on the night.
Sikeston had four players reach double figures led by sophomore Julian Beard's 13 points. Kash Bratcher had 12 points, four assists and four steals.
Rod Moore had 11 points and Tyler Woodson added 10 points.
Sikeston will play Paducah Tilghman on Thursday at 8 p.m.
The Blue Tornado (6-9) lost to Caruthersville 71-40. Caruthersville was led by Kyle Hubbard and Paul Sanders with 26 points apiece. Plessie Ellitt added 15 points.
Tilghman was led by 6-4 sophomore David Jones' 16 points.