Despite coming off a huge victory one week ago, the banged up New Orleans Saints defense takes on another formidable NFC opponent in the San Francisco 49ers on Sunday afternoon at the Superdome.

New Orleans will miss top rookie safety Kenny Vaccaro due a concussion, and fellow safeties Roman Harper and Malcolm Jenkins are also overcoming knee and hamstring issues.

Top defensive end Cameron Jordan along with inside linebacker Curtis Lofton are also nursing injuries, putting the Saints ability to thwart hard-charging 49ers running back Frank Gore in doubt. Gore headlines San Francisco’s fourth ranked rushing offense, and is seventh in the NFL with 700 rushing yards and seven touchdowns.

San Francisco suffered their third loss of the season in a brutal 10-9 loss to Carolina last week, putting them two games behind Seattle in the NFC West. A win over New Orleans could put the 49ers back on track for a top seed in the NFC, and a leg up on tiebreakers as the season winds down.

New Orleans and quarterback Drew Brees have gone 2-2 since beginning the season 5-0. In that same four-game stretch Brees has been sacked eight times and hit another 18, but has still tossed 13 of his 25 passing touchdowns.

The 49ers pass rush hasn’t been as dominant as last year’s, but they’ll welcome back linebacker Aldon Smith for the second straight game. Smith has 4.5 sacks in four games this season, and was second in the league last year with 19.5 sacks. Limited to 12 snaps last week, Smith failed to record a tackle.

Should San Francisco find a way to get to Brees, New Orleans may need another career game from third-year running back Mark Ingram, who gained a career-high 145 yards and a touchdown on 14 carries in last week’s 49-17 win over Dallas. The pass happy Saints are 23 rd in the NFL in rushing.

The 49ers offense, and in particular quarterback Colin Kaepernick, will have to show serious signs of life after gaining a paltry 151 total yards against the Panthers. Perhaps in a sophomore funk and lacking confidence, Kaepernick has only twice passed for more than 200 yards this season, and his completing 56.4 percent of his attempts for San Francisco’s last place passing game.

Kaepernick might be down tight end Vernon Davis due to a concussion, but receiver Mario Manningham is set to make his season debut. Manningham has been sidelined since last Decembeer with a knee injury, after finishing third on the team with 449 yards and 42 receptions.

However receiver Michael Crabtree will likely remain out despite participating in Friday’s practice. He probably won’t return until next week against Washington.

Betting Odds: New Orleans is favored by 3 points

Over/Under: 48 points

Time: 4:25 p.m. ET

Channel: FOX

Watch Online: NFL Sunday Ticket

Prediction: New Orleans 27, San Francisco 20