The first generation Nissan Murano caught the public's eye in 2003 as a mid-size crossover SUV. The Murano was between the Xterra and Pathfinder in the Nissan lineup of vehicles. It derived its power from a 3.5 Liter V6 engine with 245 horsepower, and was equipped with a continuously variable transmission. The Murano was available with either front-wheel or all-wheel drive. It came in two versions; the entry level SE and the SL version. It was equipped with a camera at the back, airbags, anti-lock brakes and a system to ensure that the power of the brakes was electronically delivered to all the tires.

In 2004, a satellite radio was added to the Murano, as well as the ability to shift manually in the automatic transmission. Both models now were equipped with 18 inch tires. Xenon headlights were standard equipment on the SE version while it was optional on the SL model. New options were heated front seats and a DVD system for the passengers in the back. While the Murano could now carry five passengers, there was no third row of seats. In 2005, a new entry level S model joined the lineup. A sensor was added that would inflate the airbags if the vehicle was about to roll over and both the SL and SE models came with keyless entry. In 2006, the stereo control buttons located on the vehicles steering wheel were lighted and it had a better looking grille. In 2008, the Murano is only available in the SL and SE versions.