A light sheet microscope, comprising: - illumination optics for illuminating a sample which is located on a sample carrier in a medium, the sample carrier being aligned parallel to a flat reference surface, via an illumination beam path with a light sheet whose light sheet plane encloses a non-zero illumination angle with the normal of the reference surface, - detection optics with a detection beam path with an optical axis which encloses a non-zero detection angle, in the region of the sample carrier, with the normal of the reference surface, - a separating layer system with at least one layer of a predetermined material having a predetermined thickness, which separates the medium from the illumination and detection optics, wherein the separating layer system is in contact with the medium, at least in the region accessible for illumination and detection, via a base surface aligned parallel to the reference surface, wherein - the light sheet microscope comprises means, independent of the light sheet generation, for applying light intensity to the sample in substantially point-shaped areas in the light sheet plane or in a predetermined volume at least temporarily encompassing the light sheet plane via at least one manipulation beam path, characterised in that - the means for manipulation comprise a separate manipulation objective in the manipulation beam path, which is arranged with its optical axis parallel to the normal of the reference surface, - and the light sheet microscope comprises at least one correction element in the illumination and/or detection beam path for reducing such aberrations which arise due to the oblique passage of light to be detected or of light for illuminating the sample through interfaces of the separating layer system. - illumination optics for illuminating a sample which is located on a sample carrier in a medium, the sample carrier being aligned parallel to a flat reference surface, via an illumination beam path with a light sheet whose light sheet plane encloses a non-zero illumination angle with the normal of the reference surface, - detection optics with a detection beam path with an optical axis which encloses a non-zero detection angle, in the region of the sample carrier, with the normal of the reference surface, - a separating layer system with at least one layer of a predetermined material having a predetermined thickness, which separates the medium from the illumination and detection optics, wherein the separating layer system is in contact with the medium, at least in the region accessible for illumination and detection, via a base surface aligned parallel to the reference surface, wherein - the light sheet microscope comprises means, independent of the light sheet generation, for applying light intensity to the sample in substantially point-shaped areas in the light sheet plane or in a predetermined volume at least temporarily encompassing the light sheet plane via at least one manipulation beam path, characterised in that - the means for manipulation comprise a separate manipulation objective in the manipulation beam path, which is arranged with its optical axis parallel to the normal of the reference surface, - and the light sheet microscope comprises at least one correction element in the illumination and/or detection beam path for reducing such aberrations which arise due to the oblique passage of light to be detected or of light for illuminating the sample through interfaces of the separating layer system.