Real's victory, which also featured goals from Roberto Carlos and Raul Bravo, gave them some vital breathing space in their title battle with Valencia, who were beaten 1-0 at home to resurgent Barcelona.
With the Champions League set to resume next week, Real lead the standings with 56 points from 25 games, followed by UEFA Cup hopefuls Valencia on 51.
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Barcelona's fifth successive league win, clinched when the former Valencia midfielder Gerard headed in from a corner, took them further clear in the race for the fourth Champions League qualification place with 43 points.
Celta Vigo and Real Sociedad, who will join Real Madrid and Deportivo in Champions League action next week, both suffered morale-sapping defeats.
Celta, who remain in relegation trouble, went down 2-0 at home to Malaga, while mid-table Sociedad were beaten 1-0 at Sevilla.
LUCKY BREAK
Real, who needed a controversial last-minute penalty to claim a 1-1 draw against Valencia last week, once again enjoyed the benefit of the doubt in the area when Raul went down with his back to goal midway through the first half.
There appeared to be little contact between Raul and Belgian goalkeeper Lemmens but the referee pointed to the spot and Ronaldo gratefully slotted in to put Real 1-0 up.
Espanyol were incensed but the referee helped restore parity within five minutes, ruling that Real keeper Iker Casillas had brought down Ivan de la Pena and awarding another marginal penalty that Tamudo converted.
The visitors, without the suspended David Beckham, laboured in the first half but they were back to their slick-passing best after the break and made certain of victory with three goals in 17 minutes.
Zinedine Zidane's raking pass picked out Ronaldo in the 53rd minute and the striker teed up his fellow Brazilian Roberto Carlos to sweep in for 2-1.
Raul Bravo met a corner from the right for Real's third and Ronaldo took a pass from Esteban Cambiasso and beat the keeper for the fourth in the 70th minute.
Lopo was left unmarked to score Espanyol's second six minutes from time after a poor defensive header but Real's victory was never in doubt.
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