Aim To evaluate the experience of change fatigue in frontline nursing staff following large‐scale organisational change and determine whether improved teamwork perception scores can mitigate the experience of change fatigue in this population. Background There is limited published research pertaining to the experience of change fatigue in nursing, despite the rapid rate and volume of change within health care organisations. Method An online questionnaire was used to survey a cross section of frontline nurses from two distinct cohorts; those that transitioned to a new build hospital in an established team (n = 225), and those who transitioned into a newly reconfigured team (n = 521). Results Frontline nurses who transitioned in an established team reported higher levels of change fatigue following large‐scale change, compared with those that commenced in a new, reconfigured team (p = 0.013). There is a small significant negative correlation between perception of teamwork and change fatigue scores. Conclusion(s) Regardless of team type, high levels of change fatigue are reported by frontline nursing staff following large‐scale organisational change. Established teams have a higher perceived level of teamwork in all domains when compared with a new team in the same change conditions. It is unlikely that the perception of teamwork has any real‐world impact upon the experience of change fatigue. Implications for Nursing Management Change fatigue is a real phenomena experienced by frontline nursing staff during large‐scale organisational change conditions. Investing in teamwork training prior to or during large‐scale organisational change does not affect the experience of change fatigue.