The draw in Kiev on Friday night pitted Del Bosque's men against Italy in Gdansk in the opening match of their title defence on June 10, and he is well aware of their strengths after his side lost 2-1 to the Azzurri in a friendly in Bari in August.
The Spain boss told marca.com: "It is not easy. Italy are a well-organised team, they demonstrated in Bari that they are a good side.
"Croatia and Ireland qualified with much authority in the play-offs. We must be respectful. Croatia has players playing in top clubs in Europe. I'm not saying we should be upset, but we have to prepare our best and reach for June in the best conditions."
Italy coach Cesare Prandelli will take heart from that friendly win, and has already spoken to Republic coach Giovanni Trapattoni - one of his predecessors as Italy coach - about the draw.
"Knowing Trap he'll be gunning for a prestigious position right up to the last second," Prandelli told Gazzetta dello Sport.
"At the moment there are no advantages or disadvantages, we're just thinking about going there properly prepared because you have to arrive at the tournament with the right approach.
"Trapattoni and I met today and he always manages to lighten up any atmosphere: after the draw he told me he would have to change the location of Ireland's training camp now, because he had planned to go to Montecatini (a spa resort in Tuscany)."
Prandelli is hoping to have his first-choice forward line of Antonio Cassano and Giuseppe Rossi available for the tournament, with both laid low by injuries so far this season.
"We started with them and the team found the right balance," he added.
"I hope we can get both of them back. We've looked at alternative formations and it's still early days but I'm inclined to stick with the diamond in midfield."
Group B looks the most competitive of all, with Germany, Holland, Portugal and Denmark paired together in a pool based in Kharkiv and Lviv.
Germany coach Joachim Low told his national association's official website www.dfb.de: "I think that this is the hardest, strongest and most balanced group of the tournament.
"The Netherlands and Portugal have world-class players, because we can look forward to interesting duels. Denmark is an uncomfortable tournament team. The Danes can always take the role of the underdog and thus compete against all unencumbered and unafraid. This makes them so dangerous."
Holland boss Bert van Marwijk told www.vi.nl: "All the coaches in the group had a photo together and I can say that no one looked happy.
"Actually, it seems a bit like the last World Cup when we started against Denmark. It is important to make a great start. They are three great opponents who we know well. It's a huge challenge."
Van Marwijk, who had hoped his side would be in the Poland-based Group C, added: "I'm especially sorry for the fans, who now have to travel much further. For us, it does not even really matter. It's only 15 minutes longer trips, but in the plane."
France, who were in the bottom group of seeds, are in Group D alongside England, Sweden and co-hosts Ukraine.
Les Bleus coach Laurent Blanc was quick to cast England as group favourites, and told his federation's official website www.fff.fr: "We have got an even group, where England will have the status of favourite but all four teams that comprise it are capable of qualification (for the knockout stages).
"Everyone will be keen to do well and we know that all matches will be difficult. But we will not complain, we could have been placed in Group B. The challenge there is even more tough because that pool is certainly the most complicated."
Co-hosts Poland will feel they have a chance of achieving their pre-tournament aim of reaching the last eight after being drawn alongside Greece, the Czech Republic and Russia in Group A.