Sydney will look to continue their recent run of good form against AIS, while Victory will be out to secure their first points of the campaign when they host Gold Coast.
AIS v Sydney FC AIS Athletics Park, Saturday 3pm
The AIS and Sydney FC could hardly carry any more contrasting form into their Week 6 encounter on Saturday.
The hosts are battling to avoid three consecutive losses since their only win of the season, in Week 2 against Gold Coast United.
The Sky Blues, on the other hand, venture to Canberra having hit 10 goals in their last two games.
Steve Corica's men thumped Melbourne Victory 5-1 on Sunday, with senior striker Juho Makela hitting a brace in his return from injury and midfielder Mitchell Mallia taking his season tally to seven goals with his 33rd-minute strike.
Containing the confident Sky Blues will be the AIS' first task; finding the goals to win the match - as the NYL's second-lowest scoring side - will be the second.
Adelaide United FC v Newcastle Jets FC Burton Park, Saturday 4pm
The Newcastle Jets' NYL season slipped to its lowest point after getting on the end of a 6-3 spanking by the Brisbane Roar last Sunday, and they will be keen to atone for that performance when they travel to Adelaide United.
United hardly look a picture of defensive strength either, slumping to a 4-1 defeat at re-born Gold Coast United in a forgettable Week 4 outing.
The hosts will be keen to bid farewell to a nasty November, having failed to register a point since October 29's 3-0 win at Brisbane.
One positive for the Reds is the goalscoring form of Australia Under-19 representative Liam Wooding, who hit his third goal in two games in the 3-2 loss to Perth on Saturday.
Kale Bradbery scored his own brace for the Jets after coming on as a substitute for overage attacker Ali Abbas, but shoring up things at the other end will surely be the focus for Mark Jones' men.
Melbourne Victory FC v Gold Coast United FC AAMI Park, Sunday 2.15pm
It already looks a long season ahead for Melbourne Victory, whose on-field NYL woes are not out of place alongside the dramas of their senior counterparts.
Clean sheets have been a rarity this NYL campaign, with 99 goals conceded across 24 matches played.
Victory hold the ignominious honour of shipping the most, however, having 18 goals in the against column and scoring just twice themselves in five matches.
Gold Coast United will be confident of extending Victory's poor run, with the two-time champions rediscovering their form after three losses to start their title defence.
Victory have not been helped the injury, suspension and national team duty issues of the club's senior side, with James Jeggo - among their better performers this season - a chance to again be summoned by Mehmet Durakovic.
Melbourne Heart v Central Coast Mariners John Cain Memorial Park, Sunday 2.30pm
Across town, and Melbourne Heart will be hoping to bounce back from their 3-2 loss against Gold Coast last Saturday to re-focus their ascension up the NYL table.
The return of Adrian Zahra failed to spark John Aloisi's men on the Glitter Strip, and they will need to be at their best to see off one of the competition's form sides.
The Mariners make the trek to Melbourne on the back of three-straight victories, with a sound defensive performance seeing off the AIS 3-1 on Sunday.
Captain Jimmy Oates led the Mariners well with his 63rd-minute sealer, while the likes of strikers Kwabema Appiah-Kubi and Mitchell Duke will be ones for Heart goalkeeper Sebastian Mattei to watch carefully.
Brisbane Roar FC v Perth Glory FC Cleveland Showgrounds, Sunday 3pm
In the only fixture of Week 6 to feature two sides in winning form, Perth Glory make the trip to Brisbane knowing a victory will knock their opponents from the top of the NYL table.
Having been thumped 5-2 by Sydney FC in Week 4, the Glory returned from Adelaide on Saturday with a 3-2 win after making their early domination count.
A different prospect looms on Sunday, with the Roar's NYL team emulating the form of their senior club-mates.
Brisbane smashed six goals past Newcastle last Sunday and - while they would have been disappointed to concede three - it is a sign of the attacking talent throughout the entire club.
Rocky Visconte was one to find the back of the net for the Roar as he continued his claims for senior opportunities, but it was a hat-trick to Nathan Fitzgerald that stole the show.
He will need minding by the Glory's defence, which has not kept a clean sheet since Week 1's victory over the AIS.