Town will be aiming for a 17th-placed finish when they travel to the Weston Homes Community Stadium on Saturday.
Three points in Essex would see the Glovers end the campaign on 53 points – five ahead of last year’s total.
It would see Darren Way’s side rise above Crewe Alexandra and Morecambe, should the pair drop points in their final day encounters against Barnet and Luton Town respectively.
Should that happen, Yeovil will finish two positions higher than the 2015/16 standings.
The Glovers secured their league safety with a 1-1 draw against Stevenage at Huish Park last weekend.
Jean-Louis Akpa Akpro netted his second goal in successive home games for the Green and Whites, and will be looking to add to his tally at Colchester before his loan spell from Barnet expires.
Bournemouth loan duo Ben Whitfield and Matt Butcher will bid farewell to Yeovil at Colchester, as will Swansea City pair Liam Shephard and Owain Jones, and Tottenham Hotspur youngster Shayon Harrison.
Goalkeeper Jonny Maddison is likely to end the campaign between the sticks after producing a man of the match display against play-off hopefuls Stevenage.
Colchester are also hoping to end the season in the top seven.
The U’s, who are one of seven teams looking to secure one of the last two play-off spots, are one point off seventh-placed Blackpool.
John McGreal’s outfit are unbeaten in five and have lost just two in their last nine games.
However, wide man Brennan Dickenson will prove to be a big miss for the Essex club after suffering a serious cruciate knee injury.
The 24-year-old, who is wanted by Ipswich Town, has 12 league goals to his name and seven assists.
Experienced forward Chris Porter has netted on 16 occasions this year and will continue to lead the line for the U’s.
Yeovil have never won on the road at Colchester (D4 L5).
However, the Glovers did win their last meeting against the U’s at Huish Park.
Kurtis Guthrie gave the visitors an early second-half lead before Francois Zoko looked to have rescued a point with four minutes remaining.
But up popped Tahvon Campbell in the dying embers of the contest to send a deflected effort past Sam Walker to secure Town a deserved victory.
Robert Jones will take charge of his 41st game of the season in Essex.
Mr Jones has awarded 120 yellow cards this year and has issued four reds.
The Merseyside-born officiated Town’s EFL Cup triumph at Walsall and the 1-1 draw away to Wycombe Wanderers.
He will be assisted by Joe Simpson (Manchester) and Marvyn Amphlett (Worcestershire) with Nigel Lugg (Surrey) acting as fourth official.
Darren Way and Alex Lacey’s pre-match interviews can be viewed on YTFC’s official YouTube account here.
On matchday, minute-by-minute updates will be provided on YTFC’s official Twitter account which can be found here, with additional updates available via YTFC’s official Facebook page.
If you’re unable to attend the game a full match report will follow on ytfc.net at full-time with post-match reaction from manager Darren Way and a member of the playing staff following soon after.
Fans can still purchase tickets at the Huish Park ticket office or by phone on 01935 847888. Due to the complexity of the ticketing structure, supporters cannot purchase online. The game is pay on the day. Click here for more information.