Pako Ayestaran's side currently sit 16th - just one place and one point above the relegation zone - whereas their visitors are flying high in fifth place after five games.
Tondela have flirted with relegation pretty much every season since winning promotion in 2014-15, and the beginning of the 2020-21 campaign has offered few signs that this term will be any different.
Ayestaran, who learned his trade as assistant to Rafael Benitez at Valencia and Liverpool, has endured a difficult start to life in the Tondela dugout, most recently losing 4-0 at leaders Sporting Lisbon.
There is no shame in defeat to one of Portugal's 'big three', but the result leaves Tondela hovering perilously close to the relegation zone once again, with the worst goal difference in the league to boot.
Only Belenenses have scored fewer goals than their four in six games, while only Famalicao have shipped more than Tondela's 12, which includes two 4-0 defeats already.
The victory over Portimonense in their most recent home game will offer them some cause for optimism heading into this match, although they have not won back-to-back home league games since April 2019.
The hosts face a difficult test in a Santa Clara side that is newer to the top flight than them but have seemingly adapted quicker, making steady improvements since reaching the top flight in 2017-18.
As things stand Daniel Ramos's side sit in an impressive fifth place, with 10 points from their opening six games - level with Porto.
Another victory, to follow up last weekend's win at Portimonense, would temporarily lift them up to third place - a notable achievement for Ramos early in his second stint as boss.
Recent defeats to Pacos de Ferreira and Sporting mean that Santa Clara will not be getting carried away with their start, but they will still be confident of coming away with all three points from this match.
Tondela Primeira Liga form: DLLDWL
Santa Clara Primeira Liga form: WWDLLW
Out: Ricardo Alves (muscle)
Doubtful: Andre Mesquita (muscle)
We say: Tondela 1-2 Santa Clara
Santa Clara are perhaps punching above their weight at the moment and would do very well to still be among the European spots at the end of the campaign, but given Tondela's current form we can see the visitors continuing their bright start to the season here.