A humongous AFC South showdown with some major implications on the line will take place this weekend as the Indianapolis Colts battle things out with the Jacksonville Jaguars. Let's check out our NFL odds series where our Colts-Jaguars prediction and pick will be revealed.

Coming into this high-profile matchup at 3-1 overall, the Colts stood tall on their home turf by outlasting the Tennessee Titans 23-16 in impressive fashion. A year ago, things could not have looked more bleak for a Colts squad that eventually finished 4-12 and were gifted QB Anthony Richardson in the very first round of the NFL Draft. Could the Colts make a big-time statement on Sunday with a dominant performance versus the Jaguars?

Meanwhile, Jacksonville doesn't look as formidable as they were late in the season a year ago, but they still sit at 3-2 and could find themselves with sole possession of the AFC South if they can take care of business against their longtime division foe. Most recently, it was Jacksonville that pulled off a season-defining victory overseas in London as it was the Jags that downed the contending Buffalo Bills by a score of 25-20.

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

NFL Odds: Colts-Jaguars Odds

Indianapolis Colts: +4.5 (-120)

Jacksonville Jaguars: -4.5 (-102)

Over: 44.5 (-105)

Under: 44.5 (-115)

How to Watch Colts vs. Jaguars Week 6

Time: 1:00 om ET/10:00 am PT

TV: CBS

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

Why The Colts Could Cover The Spread

In order for the Colts to treat their fans and bettors with a covering of the spread and possibly a win, this hard-nosed defense will need to come and play once again. Against a physical demanding opponent in Tennessee, it proved to be Indianapolis that put on their best impression of the Great Wall of China. By the time the clock hit triple zeroes, Indy held Derrick Henry to only 43 yards on 13 carries. Thus far, this ferocious defense could be the most improved unit in all of the NFL from last season as the Colts have only surrendered 30 points one time.

Not only will the defense need to stand firm against a more than talented Jaguars offensive attack, but gaining stability at the quarterback position for this showdown and for weeks to come will prove to be vital. After rookie field general Anthony Richardson went down with a shoulder injury, backup Gardner Minshew and his certified swag as one of the league's top second-string quarterbacks has played well in a relief role, but getting both Zack Moss and Jonathan Taylor going in the run game from the opening snap will be an absolute must.

Finally, already facing off with Jacksonville for the second time this season, the biggest thing that haunted Indianapolis in the Week 1 matchup against the Jags was the fact that turning the ball over far too often came back to bite them in the behind. Simply put, the Jags can score faster than most teams in the league, and if the Colts give them short fields by being careless with the football again, then things will be looking bleak.

Why The Jaguars Could Cover The Spread

Although Jacksonville ended up scoring only 25 points, it was the fact that the Jaguars absolutely dominated the time of possession that ended up being the most impressive feat on the day. Indeed, it appears that this offense's slow start to the regular season could be in the rearview mirror, and if that is the case, then there is no question that the Colts will have their hands full trying to halt QB Trevor Lawrence and company from moving the football down the field with ease.

Not to mention, but Jacksonville's willingness and eventual found success in running the football down the throat of the Buffalo Bills exemplified the team's toughness. In reward, the Jags ended up rushing for nearly 200 yards on the ground and took care of business within the trenches. On paper, Jacksonville loves to air it out, but staying committed to the run game could be just what the doctor ordered in terms of finding a way to cover. Staying balanced will be key folks!

Final Colts-Jaguars Prediction & Pick

The AFC South lead is officially up for grabs! This will most likely be a hotly contested contest, but not being healthy against a fully operational squad in the Jaguars will ultimately be the Colts' downfall. Alas, Jacksonville will cover the spread and also make their bettors smile from ear to ear all over the country!

Final Colts-Jaguars Prediction & Pick: Jaguars -4.5 (-102)