The world and European champions, who won their opening group match against Liechtenstein 4-0, play Lithuania in Del Bosque's home town of Salamanca on Friday and travel to Glasgow to take on Scotland on Tuesday.
"These are two key matches for us, even though you might think that they are comfortable games," Del Bosque said at a news conference at a hotel on the outskirts of Salamanca.
"We have to be prepared to encounter difficulties," he added, noting that the Lithuanians had yet to concede a goal in drawing 0-0 at home to Scotland and surprising Czech Republic 1-0 in Prague in their opening two qualifiers.
"Lithuania are a well-organised side, without any really big names but who play very well," he added.
"We know that the margin for error is tight and we have to focus on that."
The potential gulf between the sides is illustrated by the world rankings, with Spain top ahead of Netherlands, Germany and Brazil, Lithuania 42nd and Scotland 47th.
However, injuries have deprived Del Bosque of several key players, including playmakers Xavi and Cesc Fabregas and forwards Fernando Torres, Pedro and Jesus Navas.
SCORING RECORD
Del Bosque said Xavi's Barcelona team mate Andres Iniesta may take on the playmaker role against Lithuania but added that he had other options including Manchester City's David Silva and Villarreal pair Santi Cazorla and Borja Valero.
"There is no doubt that he (Xavi) is one of our best players," Del Bosque said. "But we'll try to make sure his absence is noticed as little as possible."
Speaking at an earlier news conference, central defender Gerard Pique said the players were hoping striker David Villa netted the goal he needed to draw level with Spain's record scorer Raul on 44.
Former Real Madrid striker Raul, now at Bundesliga club Schalke 04, scored his 44 goals in 102 appearances, while Villa has 43 in just 67.
"The goal-scoring ability that Villa brings to the team is very important," said Pique, who plays with Villa at Barca. "The sooner he can equal the record, so much the better."
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