Worcester boss Richard Hill has warned his players not to be distracted by the potential bigger picture against Rovigo.
The Warriors' back-to-back appointments with Perpignan in December look likely to decide which club secures a quarter-final place from Pool Two.
But Worcester have a job to do against Italian opposition first as they target another strong display following last weekend's bonus-point victory over tournament newcomers Gernika.
"We are treating this competition very seriously," Hill said.
"We need a big win this weekend and that will set us up for the two crucial matches against Perpignan.
"The danger when you come up against a weaker side is that you take them lightly and put in a bitty performance, but that won't be the case with us."
Rovigo were crushed 79-12 at home by Perpignan six days ago, and have won just three of their 49 games in European competition.
But Hill added: "Rovigo were actually leading 12-10 against Perpignan after 25 minutes before they fell away, so it was a very tight opening to that match.
"They are obviously very competitive for 20 or 30 minutes and they will take some breaking down. If we can do that, then hopefully we can do the same to them as Perpignan did.
"They will be organised and robust, but we will be expecting to secure a five-point win."
Hill hands full-back Errie Claasens his first start of the season, while Fiji international Ravai Fatiaki is named alongside Jon Clarke in midfield and Samoan wing David Lemi gains a recall.
Four changes in the pack, meanwhile, see hooker Ed Shervington given a starting berth, along with skipper Dean Schofield, flanker Sam Betty and number eight Semisi Taulava.
Like Worcester, London Irish opened Challenge Cup business in bonus point fashion, defeating Bordeaux-Begles 43-16, and they face another French rival when Mont-de-Marsan arrive at the Madejski Stadium.
Rugby director Brian Smith makes just two changes from that Pool One encounter, fielding full-back Anthony Watson instead of Steven Shingler and restoring skipper Declan Danaher to the back row.
"Mont-de-Marsan showed a lot of guts and determination last week against Gloucester," Smith said.
"We expect they will be fired up for another shot at an England-based team, and we look forward to meeting that challenge head on."
London Welsh gained a sobering introduction to European rugby last Saturday when they shipped nine tries and 68 points at home against Parisians Stade Francais.
Life should be a good deal more comfortable against Italian minnows Prato, though, whose opening fixture produced a 59-3 loss to Grenoble.
"It wasn't the best day at the office for anyone," said Exiles lock Martin Purdy, recalling the Stade Francais drubbing.
"Whether our attitude was wrong or we gave them too much respect, they pretty much beat us at every aspect of the game."
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