• We investigated dissociation and alexithymia in psychogenic non-epileptic seizures (PNES). • We compared four samples: patients with PNES, PNES with epilepsy (EP), EP and healthy controls. • Dissociative experiences Scale-II (DES-II) and Toronto alexithymia Scale-20 (TAS-20) totals did not predict TAS-20 and DES-II totals, respectively. • In PNES sample, depersonalization/derealization (Dep/Der) was fully mediated by difficulty identifying feelings (DIF) and absorption (Abs) in predicting difficulty describing feelings (DDF). • In PNES with EP sample, DEP/DER was partially mediated by ABS in predicting DDF. Several studies previously examined the role of dissociation and alexithymia in patients with psychogenic non-epileptic seizures (PNES). However, their relationship remains unclear. We administered questionnaires for dissociation (DES-II), alexithymia (TAS-20), anxiety and depression to 57 subjects: 14 patients with PNES, 13 patients with comorbid PNES and epilepsy (PNES+EP), 14 patients with EP and 16 healthy controls. For between-group comparisons we applied Chi-square test, ANOVA and Kruskal-Wallis. The Spearman correlations, hierarchical regression analyses and path models, goodness-of-fit indices and maximum-likelihood estimates of model parameters were obtained through SPSS 27 and AMOS 27. Hierarchical regression analyses showed that nor DES-II neither TAS-20 total scores were able to predict TAS-20 and DES-II total scores, respectively, possibly due to subscale score pooling. Following modification indexes of AMOS 27, in PNES sample, we found that only Depersonalization/Derealization (Dep/Der) was fully mediated by Difficulty Identifying Feelings (DIF) and Absorption (Abs) in predicting Difficulty Describing Feelings (DDF), and a partial effect of DIF and Dep/Der implement DDF, while both DIF and DDF implement Abs. In PNES+EP group, Dep/Der was able to predict DDF, with a partial mediation of Abs that predicted Externally Oriented Thinking, while DDF was able to promote Abs, and DIF effect on Abs was fully mediated by Amnesia (Amn). Our study is cross-sectional, participants were self-selected and the data were derived from self-report measures. Conclusions: In PNES, Dep/Der and DIF may play a prominent role, while in PNES+EP, Dep/Der, Abs, DIF and Amn may be involved. Clinical implications are discussed.