Injury is a serious setback for athletes and might jeopardize mental health. The aim of this study is to investigate if a mindfulness- and acceptance-based intervention can improve mindfulness (nonreactivity and acting with awareness), acceptance, and well-being, and decrease the level of symptoms of anxiety and depression. A single-case design with multiple, staggered, and nonconcurrent baselines was used. Six seriously injured athletes took part in an 8-week intervention and repeatedly completed questionnaires on all variables for the duration of the study. The results showed that, on average, there were significant clinical changes between phases in nonreactivity, well-being, and acceptance. No effect was seen in the two remaining scales. On an individual level, two participants showed effects in all scales, two participants in some of the scales, and two participants in the scale nonreactivity. Results are discussed in light of existing research, and implications for practitioners’ clinical methods are presented.