Although problem-based learning (PBL) has many advantages, it often fails to connect to the real world outside the classroom. The integration with the laboratory setting and the use of information and communication technologies (ICTs) have been proposed to address this deficiency. Multi-user virtual environments (MUVEs) like Second Life (SL) are 3D collaborative virtual environments that could act as complementary or alternative worlds for the implementation of laboratory PBL activities offering low-cost, safe, and always available environments. The aim of this study was to compare a simple laboratory PBL activity implemented in both the real and virtual worlds, in terms of learning outcome, satisfaction, and presence. The sample consisted of 150 undergraduate university students. The results show that the MUVE provided similar learning outcome and satisfaction to the real-world condition. Presence was positively correlated to satisfaction but not to the learning outcome. Finally, there are indications that the MUVE was perceived as more pleasurable and informal learning environment, while reality was perceived as more stressful.