We're back again with another prediction and pick for Week 10 in the National Football League. We head over to Florida for a matchup between first-place teams as the San Francisco 49ers (5-3) take on the Jacksonville Jaguars (6-2). Check out our NFL odds series for our 49ers-Jaguars prediction and pick.

The San Francisco 49ers have dropped to 5-3 after last week's loss, but they still remain atop the NFC West Division. After starting the season at 5-0 and looking like favorites to win the Super Bowl, the 49ers have lost their last three straight games. Now, they'll head into a tough environment as they get some of their key players back on offense.

The Jacksonville Jaguars advanced to 6-2 following a win over the Pittsburgh Steelers in their game last week. Their season has been opposite to the 49ers as they stumbled out of the gates and started 1-2. Since, they've managed to win five straight games and are beginning to look like a dangerous playoff team as the season nears its end.

Here are the 49ers-Jaguars NFL odds, courtesy of FanDuel. 

NFL Odds: 49ers-Jaguars Odds

San Francisco 49ers: -3 (-115)

Jacksonville Jaguars: +3 (-105)

Over: 45.5 (-105)

Under: 45.5 (-115)

How to Watch 49ers vs. Jaguars Week 10

Time: 1:00 p.m. ET/ 10:00 a.m. PT

TV: FOX

Stream: fuboTV (Click for free trial), NFL Sunday Ticket if out-of-market

Why The 49ers Could Cover The Spread

The San Francisco 49ers have been trending downwards since receiving a number of injuries to key players on offense. Christian McCaffrey missed some time but will be active ahead of this one and Deebo Samuel will finally return to their lineup after spending a few games on the sideline due to injury. Trent Williams has been ‘questionable' all week, but he's trending towards not suiting up for yet another game. Along with other injuries to their offensive and defensive lines, the 49ers will come into this game rather banged-up and needing desperately to turn their fortunes around.

To cover this spread as road favorites, the San Francisco 49ers defense will have to step-up in terms of stopping big plays from the Jaguars. Fred Warner has been the MVP of their team this season and he's been one of the best all-around defenders we've seen this season. He'll be the main key in stopping the dual-threat rushing attack of Travis Etienne and Trevor Lawrence. If the 49ers secondary can force Lawrence into tough throws and create a low-scoring game, they should be able to outlast the Jaguars with their rushing attack. Expect their defense to have a gritty response after letting up 31 points to the Bengals last week.

Why The Jaguars Could Cover The Spread

The Jaguars have been humming along and their offense has been one of the tougher units to contain when they're firing on all cylinders. The Steelers lost Kenny Pickett during last week's game and the Jaguars took major advantage of the loss. Travis Etienne rushed for 79 yards and Evan Engram had a solid day carving up an otherwise solid defense for the Steelers. Trevor Lawrence continues to make smart decisions with the ball and has limited his interceptions to just four on the season. They'd like to see him use his legs a bit more as he's averaging just over 25 rushing yards per game and he may have to show his wheels off with Nick Bosa tracking him down.

To win this game, the Jaguars' defense will have to have a great performance in stopping Christian McCaffrey and Deebo Samuel. With the 49ers offensive line plagued with injuries, the Jaguars have a great opportunity to put pressure on Brock Purdy and make him step outside of the pocket. On offense, they should look to establish the run early with Etienne and hope that he can break a few long runs and change field position for them. Their air attack has been lacking the last few games, so expect Trevor Lawrence to have a much better performance in this one.

Final 49ers-Jaguars Prediction & Pick

The Jaguars have been playing great football and Trevor Lawrence continues to prove himself as a winner in this league. They'll have their toughest test of the season in facing the 49ers and their offense will have their work cut out for them. If Travis Etienne can wear down this 49ers defensive front, there's no reason they shouldn't see success running the ball up the middle and away from Nick Bosa.

However, the 49ers will be returning Deebo Samuel back to action and his return should boost the morale of this offense. They've scored 17 points in each on of their last three losses, so expect their offense to wake up and produce more this time around. I expect both running games to work for both teams, but the 49ers defense will prove to be the ultimate difference. For our prediction, let's take San Francisco to get back on track with a win.

Final 49ers-Jaguars Prediction & Pick: San Francisco 49ers -3 (-115)